The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
BREAST CANCER
Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer (December 2022)
For patients with HER2-positive metastatic breast cancer, antibody-drug conjugates are available after progression on trastuzumab and a taxane, but the optimal sequence has been unclear. In the phase III Destiny-Breast03 trial among 524 patients with HER2-positive metastatic breast cancer with progression on a trastuzumab- and taxane-containing regimen, trastuzumab deruxtecan (T-DXd) improved overall survival compared with trastuzumab emtansine (T-DM1; hazard ratio 0.64) [1]. Grade ≥3 adverse events occurred in 56 percent on T-DXd and 52 percent on T-DM1. Interstitial lung disease occurred in 15 and 3 percent, respectively. Based on results of this trial, for patients with HER2-positive metastatic breast cancer that is progressive on a taxane and trastuzumab, we suggest T-DXd as next-line therapy rather than T-DM1. (See "Systemic treatment for HER2-positive metastatic breast cancer", section on 'Rationale for T-DXd over T-DM1'.)
Acupuncture in aromatase inhibitor-induced joint pain (December 2022)
For patients with breast cancer who experience aromatase inhibitor (AI)-related joint pain, a randomized trial previously demonstrated short-term improvements with acupuncture over sham acupuncture and waitlist control. Now, with longer follow-up, patients assigned to 12 weeks of acupuncture experienced a median improvement of approximately one point on a pain scale of 0 to 10 at 52 weeks compared with the other groups [2]. We consider acupuncture to be a useful adjunctive or alternative option to pharmacologic strategies in patients with breast cancer who experience AI-induced joint pain. (See "Managing the side effects of tamoxifen and aromatase inhibitors", section on 'Musculoskeletal pains and stiffness'.)
Adjuvant olaparib in high-risk, early HER2-negative breast cancer (November 2022)
For BRCA carriers with high-risk, early HER2-negative breast cancer, adjuvant treatment with the poly(ADP-ribose) polymerase inhibitor olaparib previously demonstrated progression-free survival benefits in the OlympiA trial. Now, with longer follow-up of 3.5 years, adjuvant olaparib also demonstrated an overall survival (OS) benefit (4-year OS 90 versus 86 percent) [3]. Based on these data, for BRCA carriers with early, HER2-negative breast cancer meeting high risk criteria from the OlympiA trial (table 1), we suggest adjuvant olaparib orally twice daily for one year. (See "Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer", section on 'BRCA carriers with high-risk disease'.)
Risk of second primary cancers in male breast cancer survivors (November 2022)
The risks for second primary cancers among male breast cancer survivors is being evaluated. In one study that included data from over 10,000 male breast cancer survivors, the standardized incidence ratio (SIR) of a second primary cancer, relative to healthy male controls, was 1.3; specifically, there were increased risks of colorectal (SIR 1.3), pancreatic (SIR 1.6), and thyroid (SIR 5.6) cancer [4]. Male breast cancer survivors should engage in cancer screening according to age, family history, and genetic risk factors, if present. (See "Breast cancer in men", section on 'Post-treatment surveillance'.)
Breast implant-associated cancer (October 2022)
Breast implant-associated malignancies are rare, with most concern related to breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The US Food and Drug Administration and the American Society of Plastic Surgery have recently focused on breast implant-associated squamous cell cancer (BIA-SCC), which can also occur in the capsule surrounding the implant [5]. Clinical features of BIA-SCC that differ from BIA-ALCL include its longer average time to onset after implantation, more aggressive behavior, and higher mortality. BIA-SCC is also associated with either smooth or textured implants, whereas BIA-ALCL is predominantly associated with textured implants. When treating patients who have late-onset peri-implant changes, seroma, or mass, it is essential to consider the possibility of BIA-SCC in addition to BIA-ALCL. (See "Implant-based breast reconstruction and augmentation", section on 'Squamous cell carcinoma'.)
No benefit with adjuvant ibandronate in postmenopausal women with breast cancer (September 2022)
For postmenopausal women with at least a moderate risk of breast cancer recurrence, adjuvant bisphosphonates have improved disease-free survival (DFS) outcomes in randomized trials. However, in a new randomized trial in over 1100 postmenopausal women, oral ibandronate 50 mg daily did not improve DFS relative to placebo [6,7]. Although a previous head-to-head trial that included both pre- and postmenopausal women found similar DFS outcomes with clodronate, ibandronate, and zoledronic acid, this trial is now the second in postmenopausal women to fail to show a DFS benefit from ibandronate over placebo. For patients in whom an adjuvant bisphosphonate is indicated for breast cancer, we suggest zoledronic acid or clodronate (algorithm 1), and consider ibandronate a less preferred alternative. Clodronate is not available in the United States. (See "Use of osteoclast inhibitors in early breast cancer", section on 'Choice of bisphosphonate for anticancer therapy'.)
Vaginal estrogen therapy in patients with a history of breast cancer (August 2022)
Low-dose vaginal estrogen is an effective treatment for moderate to severe symptoms of genitourinary syndrome of menopause (GSM) unresponsive to nonhormonal management (vaginal moisturizers, lubricants), but its safety in patients with breast cancer is unclear. In a study of postmenopausal patients with a history of early estrogen-positive breast cancer treated with aromatase inhibitors (AI), those who used vaginal estrogen after the breast cancer diagnosis had a higher risk of breast cancer recurrence compared with nonusers (adjusted hazard ratio 1.39, 95% CI 1.04-1.85) [8]. This association was not seen in patients treated with tamoxifen. While there are several limitations to this study, these data support our general practice of prescribing vaginal estrogen for management of GSM in patients with breast cancer treated with tamoxifen but not those treated with AI. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment", section on 'Patients with breast cancer'.)
Radiation boost for ductal carcinoma in situ (August 2022)
The use of a radiation boost to the surgical bed reduces recurrences in patients receiving whole breast radiation therapy (WBRT) for early invasive breast cancer, but its role in ductal carcinoma in situ (DCIS) is less clear. In a randomized trial in over 1600 patients with DCIS with at least one risk feature, those assigned to a radiation boost experienced five-year free-from-local-recurrence rates of 97 versus 93 percent in the no boost group (hazard ratio 0.47) [9]. For most women receiving WBRT for early breast cancer including DCIS, we suggest radiation therapy boost to the tumor bed to reduce the risk of local recurrence. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer", section on 'RT boost to the tumor bed'.)
Pembrolizumab plus chemotherapy in PD-L1 positive advanced triple negative breast cancer (July 2022)
For patients with advanced programmed cell death ligand 1 (PD-L1) positive triple negative breast cancer (TNBC), the use of an immune checkpoint inhibitor is being evaluated with chemotherapy. In a randomized trial, patients with advanced TNBCs with combined positive score (CPS) for PD-L1 expression of ≥10 experienced an improved overall survival with the addition of pembrolizumab rather than placebo to chemotherapy (23 versus 16 months) [10]. Based on these data, for those with advanced PD-L1 positive TNBC with CPS ≥10, we suggest the addition of a pembrolizumab to chemotherapy. (See "ER/PR negative, HER2-negative (triple-negative) breast cancer".)
Sacituzumab govitecan in advanced hormone receptor-positive, HER2-negative breast cancer (July 2022)
Sacituzumab govitecan is an anti-Trop-2 antibody drug conjugate that is used for advanced triple negative breast cancers; its role in hormone receptor (HR)-positive, HER2-negative disease is being evaluated. In a randomized trial in 543 patients with HR-positive, HER2-negative cancers with prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least two lines of chemotherapy for advanced breast cancer, sacituzumab govitecan improved progression-free survival compared with physician's choice chemotherapy (5.5 versus 4.0 months), with a nonsignificant trend toward improved overall survival (13.9 versus 12.3 months) [11]. Grade ≥3 treatment-emergent adverse events occurred in 74 percent on sacituzumab govitecan and 60 percent on physician's choice chemotherapy. Based on these data, we consider sacituzumab govitecan to be an appropriate later-line option for patients with heavily pretreated HR-positive, HER2–negative, endocrine-resistant advanced metastatic breast cancer. (See "Treatment of endocrine therapy resistant/refractory hormone receptor-positive, HER2-negative advanced breast cancer", section on 'Sacituzumab govitecan'.)
CANCER SCREENING AND PREVENTION
Potentially modifiable risk factors for cancer (September 2022)
Strategies to reduce cancer incidence include both screening and prevention. In a study of global cancer burden in 2019, 51 percent of worldwide cancer deaths in males and 36 percent of those in females were deemed attributable to behavioral, environmental and occupational, or metabolic risk factors [12]. Smoking was the leading cause for all adults, while other important factors included alcohol use, high body-mass index, and unsafe sexual practices. Counseling and other strategies to decrease these modifiable risk factors are an important part of preventive health. (See "Overview of cancer prevention", section on 'General lifestyle recommendations'.)
Pancreatic cancer surveillance in high-risk individuals (August 2022)
While surveillance for pancreatic cancer in high-risk individuals (HRIs) is recommended by expert groups, the long-term benefits have not been clearly established. In an analysis of 1,731 HRIs enrolled in the multicenter Cancer of Pancreas Screening (CAPS) study, 26 invasive cancers were diagnosed over a >20 year period; cases detected during surveillance were more likely to be early stage and associated with longer survival [13]. In a separate cohort study of 347 carriers of a pathogenic variant in CDKN2A who participated in a longitudinal surveillance protocol and were followed for approximately six years, 30 of the 36 pancreatic cancers detected were resectable at diagnosis; 12 were stage I [14]. Five-year survival was 32 percent in the entire cohort but among the six individuals with stage I tumors who underwent resection, five (83 percent) remained alive at three years. These studies demonstrate that early detection of potentially curable pancreatic cancer in HRIs is possible with frequent image-based surveillance, and that the numbers needed to test to detect a single case of pancreatic cancer are reasonable (194 HRIs in the CAPS analysis and 70 in CDKN2A carriers). (See "Familial risk factors for pancreatic cancer and screening of high-risk patients", section on 'Diagnostic yield, benefits, and harms'.)
Bariatric surgery and incidence and mortality from some types of cancer (August 2022)
Obesity has been associated with an increased incidence of 13 types of cancer and increased cancer-related mortality, and intentional weight loss appears to decrease these risks. In a retrospective study comparing over 5000 patients who underwent bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) with over 25,000 matched patients receiving nonsurgical care, bariatric surgery was associated with a lower risk of obesity-associated cancer (10-year cumulative incidence: 2.9 versus 4.9 percent) and cancer-related mortality (10-year cumulative incidence: 0.8 versus 1.4 percent) [15]. Substantial weight loss was required to observe a meaningful reduction in cancer risk, and greater weight loss was associated with greater risk reduction. These findings support previous data of the benefits of bariatric surgery. (See "Outcomes of bariatric surgery", section on 'Cancer risk and mortality'.)
GASTROINTESTINAL CANCER
ASCO guideline on management of metastatic colorectal cancer (November 2022)
A 2022 guideline on management of metastatic colorectal cancer is available from the American Society of Clinical Oncology (ASCO) [16]. The key recommendations include offering first-line pembrolizumab rather than cytotoxic chemotherapy to patients with deficient mismatch repair; a preference for an agent targeting the epidermal growth factor receptor rather than antiangiogenic therapy if a biologic agent is chosen for first-line therapy of RAS/BRAF wild type, left-sided primary tumors; a triplet rather than doublet chemotherapy backbone for first-line therapy of selected patients with shared decision-making; a recommendation for cytoreductive surgery plus systemic chemotherapy for selected patients with isolated peritoneal metastases; and stereotactic body radiotherapy following systemic chemotherapy for patients with oligometastatic liver metastases who are not considered appropriate for resection. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Selecting the initial therapeutic approach", section on 'Patients with deficient DNA mismatch repair/microsatellite unstable tumors' and "Locoregional methods for management and palliation in patients who present with stage IV colorectal cancer", section on 'Peritoneal carcinomatosis' and "Nonsurgical local treatment strategies for colorectal cancer liver metastases", section on 'Tumor ablation plus systemic chemotherapy'.)
Futibatinib for advanced intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or rearrangement (October 2022)
Futibatinib, a highly selective inhibitor of fibroblast growth factor receptor (FGFR) 1 to 4, has been approved by the US Food and Drug Administration for treatment of locally advanced/metastatic intrahepatic cholangiocarcinoma with an FGFR2 gene fusion or rearrangement [17]. Approval was based on the phase II FOENIX-CCA2 study, which showed an objective response rate of 42 percent, a mean duration of response of 9.5 months, and no new safety signals [18]. The most common treatment-related adverse effects were hyperphosphatemia, alopecia, dry mouth, diarrhea, dry skin, and fatigue. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'FGFR inhibitors for FGFR fusion-positive tumors'.)
Peptide receptor radioligand therapy versus sunitinib for progressive pancreatic neuroendocrine tumors (September 2022)
Therapeutic options for progressive unresectable somatostatin receptor-expressing pancreatic neuroendocrine tumors include molecularly targeted agents such as sunitinib or peptide receptor radioligand therapy (PRRT) using radiolabeled somatostatin analogs (eg, Lutetium-177 [177Lu] dotatate). In a randomized trial directly comparing 177Lu dotatate versus sunitinib in 84 patients with no prior cytotoxic or molecularly targeted therapy or PRRT, 12-month progression-free survival was twofold higher with 177Lu dotatate, and the toxicity profile was more favorable [19]. While there remains no clear consensus on optimal sequencing of therapy, the higher rates of antitumor activity and better tolerability observed with 177Lu dotatate makes this a preferable initial option rather than molecularly targeted therapy in appropriate patients, particularly those who are symptomatic from their disease. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Efficacy versus other treatments'.)
Durvalumab for locally advanced or metastatic biliary tract cancer (September 2022)
The US Food and Drug Administration has approved durvalumab, an antiprogrammed cell death ligand 1 monoclonal antibody, in combination with cisplatin and gemcitabine for adults with previously untreated locally advanced or unresectable biliary tract cancer. Approval was based on the TOPAZ-1 trial, which directly compared cisplatin and gemcitabine with or without durvalumab for up to 24 weeks; those in the durvalumab group received ongoing monthly durvalumab until disease progression or toxicity [20]. Durvalumab improved objective response rates and modestly improved median overall survival (12.8 versus 11.5 months), but more than twice as many individuals were still alive at 24 months (25 versus 10 percent). There was no added toxicity compared with chemotherapy alone. In our view, durvalumab plus cisplatin and gemcitabine is an option, but not necessarily preferred, for first-line treatment of advanced cholangiocarcinoma. We individualize decision-making based on patient preference, insurance coverage, and drug availability. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'Gemcitabine plus cisplatin and durvalumab'.)
First-line transarterial chemoembolization plus lenvatinib for advanced hepatocellular cancer (September 2022)
The optimal approach for patients with locally advanced unresectable hepatocellular cancer (HCC) is debated, especially in the setting of a large intrahepatic tumor burden or portal vein tumor thrombus (PVTT). In the Chinese phase III LAUNCH trial, which enrolled predominantly patients with hepatitis B-related HCC and advanced disease (PVTT, a large intrahepatic tumor burden, or extrahepatic spread), the combination of lenvatinib plus transarterial chemoembolization (TACE) improved survival and more than doubled the response rate compared with lenvatinib alone, but grade 3 or 4 adverse events were also more common [21]. Additional experience with lenvatinib plus TACE is needed in Western populations, where HCC is more often alcohol-related, before it can be concluded that this is a preferred approach over systemic therapy alone (especially immunotherapy-based approaches) for frontline therapy of advanced HCC. (See "Overview of treatment approaches for hepatocellular carcinoma", section on 'Lenvatinib alone or with TACE'.)
GENITOURINARY ONCOLOGY
Adjuvant pembrolizumab for resected renal cell carcinoma (September 2022)
In patients with localized clear cell renal cell carcinoma (RCC) treated with nephrectomy, adjuvant immunotherapy with pembrolizumab is an approved treatment option in the United States and Europe, but long-term studies on disease-free survival (DFS) are ongoing. In extended follow-up of a randomized trial (KEYNOTE-564) of approximately 1000 patients with clear cell RCC treated with nephrectomy, one year of adjuvant pembrolizumab continued to improve DFS compared with placebo (30-month DFS 75 versus 66 percent) and was well tolerated [22]. Based on these data, we continue to suggest adjuvant pembrolizumab for those with resected clear cell RCC who are at intermediate-high or high risk for disease recurrence following nephrectomy. (See "Overview of the treatment of renal cell carcinoma", section on 'Approach to adjuvant therapy' and "Overview of the treatment of renal cell carcinoma", section on 'Pembrolizumab'.)
Lutetium Lu 177 vipivotide tetraxetan in metastatic castration-resistant prostate cancer (June 2022)
Lutetium Lu 177 vipivotide tetraxetan (177-Lu, formerly 177-Lu-PSMA-617) was approved by the US Food and Drug Administration for treatment of prostate-specific membrane antigen (PSMA) expressing metastatic castration-resistant prostate cancer (mCRPC) previously treated with androgen-receptor pathway inhibitors (ARPIs) and taxane-based chemotherapy on the basis of improved survival over second-line hormone therapy, but few trials have compared this agent with other survival-prolonging agents in CRPC. In the latest analysis of the phase II ANZUP 1603 trial comparing 177-Lu with cabazitaxel in 200 males with PSMA-positive mCRPC previously treated with ARPIs and docetaxel, 177-Lu provided a higher likelihood of a PSA response, similar overall survival, fewer adverse events, and better patient-reported outcomes [23]. For most males with PSMA-expressing mCRPC, we suggest 177-Lu rather than cabazitaxel after failure of ARPIs and docetaxel. (See "Overview of the treatment of castration-resistant prostate cancer (CRPC)", section on 'Radioligand therapy for PSMA-positive tumors'.)
GYNECOLOGIC ONCOLOGY
Rucaparib maintenance in newly diagnosed ovarian cancer (December 2022)
For newly diagnosed advanced ovarian cancer with response to platinum-based chemotherapy, maintenance with the poly(ADP-ribose) polymerase (PARP) inhibitor niraparib improves progression-free survival (PFS), but trials are evaluating other PARP inhibitors. In a trial in 538 patients with newly diagnosed stage III to IV, high-grade ovarian cancer undergoing surgical cytoreduction and responding to platinum-doublet chemotherapy, rucaparib maintenance improved PFS relative to placebo (20 versus 9.2 months) [24]. PFS benefits were observed both in homologous repair deficient (HRD) tumors and those lacking HRD, although benefits were lesser in this group. We await regulatory approval prior to using rucaparib maintenance in newly diagnosed ovarian cancer. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer", section on 'Efficacy'.)
Mirvetuximab soravtansine in platinum-resistant epithelial ovarian cancer (November 2022)
Mirvetuximab soravtansine is a folate receptor alpha-directed antibody and microtubule inhibitor conjugate that has regulatory approval in the United States for folate receptor-alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) that has previously been treated with one to three prior systemic treatment regimens [25]. In an earlier randomized trial in patients with platinum-resistant EOC, the agent resulted in a nonsignificant trend towards better progression-free survival compared with investigator's choice chemotherapy in those with folate receptor-alpha high tumors (hazard ratio 0.69), with better tolerability. We consider mirvetuximab soravtansine to be an appropriate later-line option in platinum-resistant EOC. (See "Medical treatment for relapsed epithelial ovarian, fallopian tube, or peritoneal cancer: Platinum-resistant disease", section on 'Other agents'.)
Doxorubicin and trabectedin as first-line therapy for advanced leiomyosarcoma (October 2022)
The combination of doxorubicin plus trabectedin holds promise in metastatic leiomyosarcoma (LMS). In a randomized trial including 150 patients with metastatic leiomyosarcoma of uterine or nonuterine soft tissue sarcoma origin, progression-free survival was longer in patients assigned to doxorubicin plus trabectedin followed by trabectedin versus doxorubicin alone (12.2 versus 6.2 months, adjusted hazard ratio 0.41) [26]. Improvements were noted in both the nonuterine and uterine subgroups. The most common grade ≥3 adverse events with and without trabectedin were neutropenia (80 versus 13 percent), anemia (31 versus 5 percent), thrombocytopenia (47 versus 0 percent), and febrile neutropenia (28 versus 9 percent). We consider doxorubicin plus trabectedin followed by trabectedin to be an acceptable option for the initial treatment of fit patients with advanced LMS. (See "Treatment and prognosis of uterine leiomyosarcoma", section on 'In combination with trabectedin'.)
Pelvic intensity modulated radiation therapy in gynecologic cancers (August 2022)
Intensity modulated radiation therapy (IMRT) is an advanced form of radiation that changes the intensity of radiation in different parts of a single radiation beam. In a randomized trial of 289 patients with endometrial or cervical cancer receiving pelvic radiation, those in the IMRT arm experienced less high-level diarrhea compared with conventional radiation therapy at one year following radiation therapy (6 versus 15 percent) [27]. Moreover, at three years, patients in the IMRT arm experienced improvements in urinary function, while those in the conventional radiation arm reported a decline in function. These data add support for use of IMRT in gynecologic malignancies. (See "Radiation therapy techniques in cancer treatment", section on 'Intensity-modulated radiation therapy'.)
HEAD AND NECK CANCER
Docetaxel for concurrent chemoradiation in head and neck cancer (August 2022)
Cisplatin is the chemosensitizer of choice for patients with non-human papillomavirus (HPV) associated squamous cell carcinoma of the head and neck (HNSCC) treated with chemoradiation (CRT), but the optimal agent for cisplatin-ineligible patients is not established. In a phase III trial of over 350 such patients with locoregionally advanced, mostly non-HPV associated HNSCC, the addition of docetaxel to radiation therapy improved two-year disease-free survival (42 versus 30 months) and overall survival (51 versus 42 months) but increased grade ≥3 toxicity (eg, mucositis, odynophagia, dysphagia) [28]. For patients with non-HPV associated HNSCC who receive definitive CRT but are ineligible for cisplatin, docetaxel is an option; the choice between docetaxel and other chemosensitizers (eg, carboplatin-based regimens) is based upon clinician preference, patient characteristics, and toxicity profile. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Docetaxel'.)
Weekly versus bolus cisplatin for definitive chemoradiation in head and neck cancer (August 2022)
For patients with squamous cell carcinoma of the head and neck (HNSCC), chemoradiation therapy (CRT) with cisplatin is the standard of care, but the optimal schedule (bolus dosing of 100 mg/m2 every three weeks versus weekly dosing of 40 mg/m2) remains under investigation. In a phase III trial (conCERT) of almost 300 patients with mostly non-human papillomavirus (HPV)-associated, locally advanced HNSCC treated with definitive CRT, weekly cisplatin had similar two-year locoregional control (53 versus 47 percent) and was less toxic compared with bolus cisplatin [29]. Based on these data, for patients with non-HPV-associated HNSCC who receive cisplatin for definitive CRT, we continue to suggest weekly rather than bolus dosing. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Cisplatin'.)
Gemcitabine plus cisplatin in locally advanced nasopharyngeal carcinoma (August 2022)
For patients with locally advanced nasopharyngeal carcinoma (LANPC), induction chemotherapy with gemcitabine plus cisplatin followed by chemoradiation is the standard of care, but long-term follow-up of overall survival (OS) was not previously reported. In the final analysis of a phase III trial of almost 500 patients with newly diagnosed LANPC, the addition of induction chemotherapy with gemcitabine plus cisplatin to chemoradiation improved five-year OS (88 versus 79 percent) and did not worsen late toxicities [30]. Based on these data, for patients with LANPC who are candidates for induction chemotherapy, we continue to suggest the use of gemcitabine plus cisplatin over other regimens. (See "Treatment of early and locoregionally advanced nasopharyngeal carcinoma", section on 'Induction chemotherapy'.)
Radiation therapy for low-risk, locoregionally advanced nasopharyngeal carcinoma (August 2022, Modified August 2022)
For patients with locoregionally advanced nasopharyngeal carcinoma (NPC) at low-risk for disease recurrence, clinical trials comparing cisplatin-based chemoradiation [CRT] and radiation [RT] alone were previously limited. In a randomized trial in almost 400 patients with stage II or stage III T3N0M0 NPC with low-risk features, RT and CRT had similar rates of three-year failure-free survival (91 versus 92 percent) and overall survival (98 versus 99 percent), but RT was better tolerated [31]. Based on these data, for patients with stage II or T3N0 (stage III) NPC at low risk for disease recurrence, we suggest RT rather than CRT but consider CRT a reasonable alternative pending longer-term data. (See "Treatment of early and locoregionally advanced nasopharyngeal carcinoma", section on 'Low-risk stage II disease'.)
MELANOMA AND OTHER SKIN CANCER
Adjuvant nivolumab for high-risk node-negative melanoma (December 2022)
In patients with resected, high-risk node-negative (stage IIB and IIC) cutaneous melanoma, one year of adjuvant pembrolizumab reduces recurrence risk, but studies are evaluating other immune checkpoint inhibitors. In an open-label phase III trial (CheckMate-76K) of almost 800 patients with resected stage IIB and IIC melanoma, one year of adjuvant nivolumab improved one-year recurrence-free survival over placebo (89 versus 79 percent) and was well tolerated [32]. Based on these data, for patients with high-risk node-negative (stage IIB and IIC) cutaneous melanoma, we suggest one year of adjuvant immunotherapy with either pembrolizumab or nivolumab. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma", section on 'Adjuvant nivolumab'.)
Nivolumab plus ipilimumab for advanced Merkel cell carcinoma (November 2022)
There are limited effective treatment options for patients with metastatic Merkel cell carcinoma (MCC) who progress on single-agent immunotherapy. In a phase II study in patients with advanced or metastatic MCC, in a subset of 12 patients with disease refractory to single-agent immunotherapy, nivolumab plus ipilimumab demonstrated objective and complete response rate of 42 and 25 percent, respectively [33]. Based on these data, we suggest combination immunotherapy with nivolumab plus ipilimumab rather than chemotherapy for patients with metastatic MCC who progress on single-agent immunotherapy. (See "Treatment of recurrent and metastatic Merkel cell carcinoma", section on 'Nivolumab plus ipilimumab'.)
Neoadjuvant pembrolizumab for high-risk, node-positive melanoma (November 2022)
For patients with high-risk node-positive (Stage IIIB, IIIC, IIID) melanoma, neoadjuvant immunotherapy was effective in phase I and II trials, but randomized studies comparing this approach with adjuvant immunotherapy, the standard of care, were previously lacking. In a phase III trial of over 300 patients with resectable macroscopic stage IIIB-IV melanoma, neoadjuvant pembrolizumab improved two-year event-free survival (72 versus 49 percent) compared with primary surgical resection followed by adjuvant pembrolizumab [34]. Overall survival data are not mature. Based on these data, for patients with high-risk node-positive (stage IIIB, IIIC, IIID) melanoma and macroscopic disease that is resectable, we suggest initial therapy with neoadjuvant pembrolizumab rather than primary surgery. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma", section on 'Macroscopic disease'.)
Adjuvant nivolumab plus ipilimumab for metastatic melanoma (November 2022)
For patients with metastatic melanoma who have undergone definitive treatment of all sites of disease, adjuvant nivolumab plus ipilimumab improves recurrence-free survival (RFS), but data on overall survival (OS) were previously unavailable. In final results of a randomized phase II trial (IMMUNED) of approximately 170 patients with metastatic melanoma and no evidence of disease after local therapy, adjuvant nivolumab plus ipilimumab improved four-year OS compared with placebo (84 versus 63 percent) [35]. The combination also improved RFS when compared with placebo (64 versus 15 percent) and nivolumab monotherapy (64 versus 31 percent). Based on these data, in patients with metastatic melanoma who have undergone definitive treatment, we continue to suggest adjuvant nivolumab plus ipilimumab for four doses followed by maintenance nivolumab to complete one year of therapy rather than surveillance alone. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma", section on 'Adjuvant nivolumab plus ipilimumab'.)
Adjuvant pembrolizumab for resected cutaneous melanoma (November 2022)
Adjuvant pembrolizumab has regulatory approval for patients with resected, high-risk, node-negative (Stage IIB and IIC) cutaneous melanoma, but long-term follow-up outcomes are limited. In extended follow-up of a phase III trial of almost 1000 patients with resected Stage IIB and IIC disease, pembrolizumab improved distant metastasis-free survival (88 versus 82 percent) and recurrence-free survival (81 versus 73 percent) at two years [36]. Based on these data, we continue to suggest the use of adjuvant pembrolizumab for patients with Stage IIB and IIC melanoma after complete resection. (See "Adjuvant and neoadjuvant therapy for cutaneous melanoma", section on 'Adjuvant pembrolizumab'.)
Neoadjuvant cemiplimab for cutaneous squamous cell carcinoma (October 2022)
For patients with locally advanced cutaneous squamous cell carcinoma (SCC), the efficacy of neoadjuvant immunotherapy was not previously established. In a study of approximately 80 patients with resectable stage II, III, or IV cutaneous SCC, neoadjuvant cemiplimab followed by surgery resulted in a pathologic complete response rate of 51 percent and objective response rate of 68 percent [37]. It also reduced surgical morbidity in some patients (eg, orbital sparing). Based on these data, for patients with resectable cutaneous SCC at risk for significant surgical morbidity or disfigurement, we suggest neoadjuvant cemiplimab followed by surgery rather than surgery alone. (See "Systemic treatment of advanced basal cell and cutaneous squamous cell carcinomas not amenable to local therapies", section on 'Surgical resection after immunotherapy'.)
NEUROONCOLOGY
Role of pneumocystis pneumonia prophylaxis with temozolomide (December 2022)
Patients with glioblastoma treated with daily temozolomide can develop pneumocystis pneumonia as a result of selective lymphopenia, but rates are not well characterized and use of antimicrobial prophylaxis in the neuro-oncology community is variable.
●In a population-based study that included more than 5000 Canadian patients with gliomas treated with temozolomide chemoradiotherapy, the incidence of pneumocystis pneumonia within one year of treatment was low (0.74 percent) and there were few infection-related deaths [38].
●In a related case-control study, the absolute risk reduction associated with prophylaxis was low (estimated number needed to treat to prevent one infection = 288), while the risk of grade 3/4 neutropenia was elevated (number needed to harm = 34) [39].
We suggest pneumocystis prophylaxis during chemoradiation in patients with glioblastoma who have additional risk factors for opportunistic infection (eg, glucocorticoid use, lymphopenia); in others, risks of prophylaxis may outweigh benefits. (See "Initial treatment and prognosis of IDH-wildtype glioblastoma in adults", section on 'Pneumocystis prophylaxis'.)
Guideline on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors (October 2022)
A new multinational guideline is available on the diagnosis and treatment of rare glial and neuronal tumors in children and adults [40]. Over 20 tumors are included in the guideline, corresponding to the 2021 update of the World Health Organization classification of central nervous system tumors. Surgery is the cornerstone of management for nearly all of these tumors, and radiation therapy is used selectively in the adjuvant and recurrent/refractory setting. Relevant molecular markers and targeted therapies are also reviewed. (See "Uncommon brain tumors", section on 'Circumscribed astrocytic gliomas'.)
Proton craniospinal irradiation in patients with solid tumor leptomeningeal disease (October 2022)
For patients with leptomeningeal disease (LMD) from solid tumors, craniospinal irradiation (CSI) with photons is typically not appropriate due to high risk of toxicity and low likelihood of meaningful benefit. However, proton CSI has an improved toxicity profile compared with photon CSI, and there has been renewed interest in its role. In a randomized phase II trial of proton CSI versus involved field radiation in 63 patients with LMD from either breast cancer or non-small cell lung cancer, proton CSI improved both median central nervous system progression-free survival (7.5 versus 2.3 months) and overall survival (9.9 versus 7.5 months) compared with involved field radiation, with no difference in the rate of serious adverse effects [41]. Although more data are needed, where available, proton CSI is an option in selected patients with LMD who have adequate functional status and controlled systemic disease. (See "Treatment of leptomeningeal disease from solid tumors", section on 'Proton craniospinal radiation'.)
Long-term follow-up of grade 3 oligodendroglial brain tumor trials (August 2022)
Final, long-term results from two cooperative group randomized phase III trials of radiation therapy (RT) with or without PCV (procarbazine, lomustine, and vincristine) chemotherapy in patients with grade 3 oligodendroglial tumors initiated in the 1990s have been published [42]. With a median follow-up of 18 to 19 years, 37 percent of patients with isocitrate dehydrogenase (IDH)-mutant, 1p19q-codeleted grade 3 tumors in each trial were predicted to be alive at 20 years after initial combined RT plus PCV, compared with approximately 15 percent in the RT alone groups. A nonsignificant trend towards benefit of PCV was observed in patients with IDH-mutant, noncodeleted tumors. These trials provide strong, complementary evidence supporting RT plus chemotherapy as the standard of care in patients with grade 3 oligodendrogliomas after maximal safe resection. (See "Treatment and prognosis of IDH-mutant, 1p/19q-codeleted oligodendrogliomas in adults", section on 'Rationale for RT plus chemotherapy'.)
PALLIATIVE AND SUPPORTIVE CARE
Lack of benefit of CBD oil for relief of symptoms in advanced cancer (December 2022)
Cannabidiol (CBD) is a naturally occurring molecule without psychoactive properties that can be procured by patients from legal marijuana dispensaries, online companies, or street suppliers. Although CBD oil is used by patients for a variety of conditions, there are few data on the risks and benefits in patients with cancer. A single phase II randomized trial of CBD oil for relief of symptoms in advanced cancer concluded that, compared with placebo, CBD oil did not add value to the reduction in symptom distress (including pain, nausea, vomiting, appetite loss, depression, or anxiety) provided by specialist palliative care [43]. Use of CBD oil cannot be recommended for symptom management in advanced cancer. (See "Management of poorly controlled or breakthrough chemotherapy-induced nausea and vomiting in adults", section on 'CBD oil' and "Management of cancer anorexia/cachexia", section on 'Cannabis and cannabinoids' and "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Choosing an agent for a therapeutic trial'.)
Eflapegrastim for chemotherapy-induced neutropenia (September 2022)
The US Food and Drug Administration has approved eflapegrastim, a novel long-acting formulation of granulocyte colony stimulating factor (G-CSF), to decrease the incidence of infection in adult patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia [44]. Approval was based on two separate trials of patients with early-stage breast cancer treated with docetaxel plus cyclophosphamide and randomized to eflapegrastim or pegfilgrastim. Efficacy was comparable, but despite the lower G-CSF dose with eflapegrastim, the incidence of adverse events (ie, bone pain, injection site reactions) was not lower in either trial. Given the available data, these two medications appear clinically similar, and agent selection may depend largely on institutional formulary and insurance constraints. (See "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation", section on 'Eflapegrastim'.)
SOFT TISSUE AND BONE TUMORS
Chemotherapy for localized Ewing sarcoma (December 2022)
For patients with localized Ewing sarcoma (ES), vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide plus etoposide (VDC/IE) is used in the United States as neoadjuvant therapy, while vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) is used in Europe. In a randomized phase III trial (EE2012) of over 600 patients with ES, initial treatment with VDC/IE improved overall survival over VIDE (three-year overall survival 82 versus 75 percent), reduced rates of grade ≥3 febrile neutropenia (58 versus 74 percent), and shortened treatment duration by two months [45]. Based on these data, for patients with localized ES, we recommend initial chemotherapy with VDC/IE rather than VIDE. (See "Treatment of Ewing sarcoma", section on 'Selection of therapy'.)
Nirogacestat for desmoid tumors (October 2022)
Desmoid tumors are a locally aggressive soft tissue sarcoma that can cause significant morbidity, and there is interest in investigating novel agents for this disease. In a randomized, placebo-controlled trial (DeFi) of almost 150 patients with desmoid tumors, nirogacestat, a gamma secretase inhibitor, improved progression-free survival (not reached versus 15 months) as well as objective response rates (41 versus 8 percent) and reduced tumor-related symptom burden and pain [46]. These data are promising, and we await regulatory approval of nirogacestat prior to incorporating its use into routine clinical practice. (See "Desmoid tumors: Systemic therapy", section on 'Nirogacestat'.)
Pimitespib for advanced gastrointestinal stromal tumors (October 2022)
For patients with advanced gastrointestinal stromal tumors (GIST) who have progressed on multiple tyrosine kinase inhibitors, there is interest in novel targeted agents. In a phase III trial in almost 90 patients with advanced GIST refractory to imatinib, sunitinib, and regorafenib, the heat-shock protein 90 inhibitor pimitespib improved median progression-free survival (2.8 versus 1.4 months) compared with placebo, as well as cross-over-adjusted median overall survival (14 versus 8 months) [47]. For patients with advanced GIST refractory to imatinib, sunitinib, and regorafenib, pimitespib is an acceptable treatment option, but is available only in Japan. (See "Tyrosine kinase inhibitor therapy for advanced gastrointestinal stromal tumors", section on 'Pimitespib'.)
Crizotinib for ALK-positive inflammatory myofibroblastic tumor (August 2022)
Inflammatory myofibroblastic tumor (IMT) is a rare chemotherapy-resistant sarcoma, and there is interest in novel targeted therapies for patients with advanced disease. In two separate open-label phase I/II trials in patients with unresectable, recurrent, or refractory IMT harboring an ALK gene rearrangement, crizotinib demonstrated objective response rates of 86 percent among children (12 of 14 patients) and 71 percent among adults (5 of 7 patients) with no new toxicity signals [48]. Based on these data, the US Food and Drug Administration approved crizotinib for adult and pediatric patients with unresectable, recurrent, or refractory IMT harboring an ALK gene rearrangement, and we also suggest initial treatment with crizotinib in this population. (See "Uncommon sarcoma subtypes", section on 'ALK-mutated tumors'.)
Chemotherapy regimens for recurrent Ewing sarcoma (July 2022)
For patients with recurrent Ewing sarcoma (EWS), randomized trials evaluating the optimal chemotherapy regimen were previously limited. In an open-label phase II/III trial (rEECur), among over 270 patients with recurrent or primary refractory EWS, event-free survival was 6 months for high-dose ifosfamide, 4 months for topotecan plus cyclophosphamide (TC), and 5 months for irinotecan plus temozolomide (IT); the IT arm had limited follow-up, as this treatment was dropped due to low likelihood of superiority [49]. Overall survival was 15 months for high-dose ifosfamide, 11 months for TC, and 14 months for IT, again with shorter follow-up for IT. Based on these data, for patients with recurrent EWS, we suggest either high-dose ifosfamide or IT, but consider TC an appropriate alternative. (See "Treatment of Ewing sarcoma", section on 'Chemotherapy'.)
THORACIC ONCOLOGY
Adjuvant pembrolizumab in resected NSCLC (December 2022)
Although adjuvant atezolizumab is used in select cases of resected non-small cell lung cancer (NSCLC), trials are examining other immune checkpoint inhibitors in this setting. In the PEARLS/KEYNOTE-091 trial, among almost 1200 patients with completely resected stage IB (T ≥4 cm) to IIIA NSCLC, adjuvant pembrolizumab improved disease-free survival relative to placebo in the overall group (54 versus 42 months; hazard ratio [HR] 0.76), with a nonsignificant trend toward improvement in those with tumor programmed cell death ligand 1 (PD-L1) ≥50 percent (median not reached in either arm; HR 0.82) [50]. Overall survival results were immature at a median follow up of 36 months. We await further data and regulatory approval prior to routine use of adjuvant pembrolizumab in resected NSCLC. (See "Systemic therapy in resectable non-small cell lung cancer", section on 'Adjuvant immunotherapy'.)
Immune checkpoint inhibitor combinations plus chemotherapy in advanced NSCLC (November 2022)
The addition of immune checkpoint inhibitors to chemotherapy improves survival in advanced non-small cell lung cancer (NSCLC), with new combinations being investigated. In preliminary results of Study 16113, among 466 patients randomly assigned to chemotherapy with or without cemiplimab, the cemiplimab group experienced an improvement in median overall survival (22 versus 13 months), with low rates of serious adverse events [51]. Similarly, in the POSEIDON trial, the addition of tremelimumab plus durvalumab to chemotherapy improved median survival (15 versus 11 months), with acceptable rates of grade ≥3 toxicity [52]. These results have led to US Food and Drug Administration approvals of combinations of cemiplimab as well as tremelimumab/durvalumab with chemotherapy in advanced NSCLC lacking certain driver mutations. (See "Management of advanced non-small cell lung cancer lacking a driver mutation: Immunotherapy", section on 'Cemiplimab plus chemotherapy'.)
Serplulimab in extensive-stage small cell lung cancer (October 2022)
In extensive-stage small cell lung cancer (ES-SCLC), the addition of either atezolizumab or durvalumab to platinum-based induction chemotherapy has improved survival; trials are exploring the use of other checkpoint inhibitors. In a randomized trial including 585 patients with treatment-naïve, extensive-stage SCLC, the addition of serplulimab to chemotherapy improved overall survival (15.4 versus 10.9 months), with modestly higher incidence of grade ≥3 adverse events (33 versus 28 percent) [53]. We await regulatory approval prior to incorporating serplulimab into treatment for ES-SCLC. (See "Extensive-stage small cell lung cancer: Initial management", section on 'Other combinations'.)
Chest radiograph versus CT surveillance after treatment of NSCLC (September 2022)
The optimal method for surveillance following treatment of non-small cell lung cancer (NSCLC) is being evaluated. In an open-label randomized trial in patients with stage I to IIIA NSCLC who had undergone surgery, those randomly assigned to computed tomography (CT)-based follow-up experienced a median overall survival of 8.5 versus 10.3 years among those assigned to chest radiograph follow-up, a difference that was not statistically significant (hazard ratio 0.95) [54]. Recurrence was detected in 33 percent in the CT-based follow-up group and 28 percent in the radiograph group; second primary lung cancers were detected in 4.5 and 3.0 percent, respectively. Although these and other data do not show survival benefits with surveillance CT after surgery for NSCLC, we perform a chest CT every six months during the first two years after treatment and annually thereafter to assist in early detection of recurrences and second primary lung cancers. (See "Management of stage I and stage II non-small cell lung cancer", section on 'Efficacy of surveillance'.)
Updated prognostic tool for patients with lung cancer brain metastases (September 2022)
The diagnosis-specific graded prognostic assessment (GPA) provides survival estimates for patients with newly diagnosed brain metastases based on analysis of thousands of patients in a multicenter database. In an updated study of patients with brain metastases from lung cancer, programmed cell death ligand 1 (PD-L1) positivity (in the primary lung tumor) was identified as an additional factor associated with improved survival in patients with non-small cell lung cancer (NSCLC) adenocarcinoma [55]. With PD-L1 status included as a variable, median survival estimates for GPA groups 1 to 4 were 6, 15, 30, and 52 months, respectively (17 months overall). A revised NSCLC non-adenocarcinoma GPA and a new small cell lung cancer GPA were also provided. Updated calculators are publicly available online. (See "Overview of the treatment of brain metastases", section on 'Prognostic assessment'.)
Retreatment with immune checkpoint inhibitors in advanced NSCLC (August 2022)
Studies are evaluating retreatment with immune checkpoint inhibitors (ICI) in patients with progression of advanced non-small cell lung cancer (NSCLC). In a retrospective study of 59 patients with advanced NSCLC who had experienced clinical benefit with prior ICI therapy followed by subsequent progression, nivolumab retreatment demonstrated an objective response rate of 8.5 percent (five patients) [56]. On multivariate analysis, ICI-free interval was a predictive factor of progression-free survival (hazard ratio 2.0). For most patients who have experienced progression after ICIs, we suggest chemotherapy; however, if progression occurs at least six months after the last dose of ICI, rechallenge may be attempted. (See "Management of advanced non-small cell lung cancer lacking a driver mutation: Immunotherapy", section on 'Managing resistance to PD-1 axis inhibitors'.)
MISCELLANEOUS TUMORS
Preoperative chemotherapy in bilateral Wilms tumor (November 2022)
Studies are investigating the strategy of preoperative chemotherapy followed by kidney parenchymal-sparing resection for patients with bilateral Wilms tumor. In long-term follow-up of a single arm, prospective study in almost 200 patients with bilateral Wilms tumor, this strategy was associated with a four-year overall survival rate of 95 percent [57]. It was greater for those with low-risk disease, intermediate-risk disease, and blastemal-type tumors than for those with high-risk diffuse anaplasia (>90 versus 72 percent). Fewer than 3 percent of patients required bilateral nephrectomy. For patients with bilateral Wilms tumor, we continue to suggest preoperative chemotherapy followed by kidney parenchymal-sparing resection rather than more extensive bilateral kidney resection. (See "Treatment and prognosis of Wilms tumor", section on 'Bilateral kidney involvement'.)
Tissue-agnostic approval of selpercatinib for RET fusion-positive solid tumors (November 2022)
Selpercatinib has received a tissue-agnostic, accelerated approval from the US Food and Drug Administration for treatment of adult patients with locally advanced or metastatic solid tumors and a rearranged during transfection (RET) gene fusion with disease progression on or following prior systemic treatment or those who have no satisfactory alternative treatment options. Approval was based on the phase 1/2 LIBRETTO-001 basket trial of 41 patients with a variety of solid tumors containing an RET fusion gene, in which the objective response rate was 44 percent and median duration of response was 24.5 months [58]. The most common grade 3 or worse treatment-emergent adverse events were hypertension and elevated serum transaminases. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Approach to later lines of systemic therapy", section on 'RET fusion-positive tumors' and "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease", section on 'RET fusion-positive tumors'.)
Sodium thiosulfate to reduce cisplatin ototoxicity in children with nonmetastatic solid tumors (September 2022)
Sodium thiosulfate (STS) has been approved by the US Food and Drug Administration to decrease the risk of cisplatin-related ototoxicity in pediatric patients aged 1 month or older with a localized, nonmetastatic solid malignancy [59]. Approval was based on two randomized trials, the Children's Oncology Group ACCL0431 trial and the SIOPEL-6 trial, which both demonstrated a lower incidence of ototoxicity among children treated with STS in the setting of hepatoblastoma or a solid tumor including germ cell cancer, medulloblastoma, neuroblastoma, or osteosarcoma. Given ongoing concerns about possible inferior oncologic outcomes, the approval was not extended to individuals with a metastatic solid tumor. The approved dose is based on actual body weight, as outlined in the US prescribing information [60]. (See "Overview of neurologic complications of platinum-based chemotherapy", section on 'Strategies'.)
OTHER ONCOLOGY
No role for statin therapy in preventing anthracycline cardiotoxicity (December 2022)
Cardiac toxicity caused by anthracycline-based chemotherapy is a major complication of cancer treatment, and there is an unmet need to identify therapies that attenuate this toxicity. In a recent trial that included nearly 300 patients who were treated with doxorubicin for either lymphoma or breast cancer and who had normal left ventricular ejection fraction (LVEF), patients randomly assigned to statin therapy or to placebo had similar decreases in LVEF after 24 months [61]. The trial used the gold standard of cardiovascular magnetic resonance imaging to quantify LVEF but was limited by missing LVEF values in more than one-third of participants. These findings do not support a role for statin therapy in preventing anthracycline-induced left ventricular systolic dysfunction; our approach to mitigating anthracycline cardiotoxicity includes limiting the cumulative dose of anthracycline and monitoring for early signs of toxicity with echocardiography. (See "Risk and prevention of anthracycline cardiotoxicity", section on 'Primary prevention with cardiovascular drugs'.)
Booster doses with the bivalent COVID-19 mRNA vaccines (September 2022, Modified December 2022)
Booster doses of COVID-19 vaccines are a strategy to improve effectiveness in the setting of waning immunity and immune evasion from circulating SARS-CoV-2 variants. The US Food and Drug Administration authorized two bivalent mRNA booster vaccines that target the spike proteins of both the original SARS-CoV-2 strain and the Omicron B.4/B.5 variants (figure 1 and figure 2) [62,63]. The Centers for Disease Control and Prevention (CDC) now recommends that all individuals ≥5 years old who have completed a primary COVID-19 vaccine series (including those who already received booster doses with monovalent vaccines) receive a single booster dose with one of the bivalent vaccines at least two months after the last vaccine dose; bivalent booster recommendations for children younger than five years old depend on the primary series vaccine received (table 2) [64]. Our approach is consistent with CDC recommendations. Although clinical data evaluating bivalent vaccines are limited, their use is supported by indirect evidence from trials and observational studies in which monovalent booster doses improved vaccine efficacy against infection and severe disease and by studies that indicate at least comparable immunogenicity with bivalent versus monovalent formulations. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations'.)
Prenatal cell-free screening results and maternal malignancy (August 2022)
In pregnant patients with a malignancy, noninvasive fetal aneuploidy screening with cell-free DNA (cfDNA) may detect circulating cfDNA from the tumor in addition to the usual placental and maternal cfDNA. In a study including over 168,000 pregnant patients who underwent prenatal genome-wide cfDNA screening, malignancy-suspicious results (ie, multiple chromosome imbalances) led to a new diagnosis of malignancy in 16 patients [65]. The appropriate clinical evaluation of malignancy-suspicious prenatal cfDNA results is unclear, in part because the results have no correlation with the tissue of origin of the malignancy. Patients undergoing prenatal fetal aneuploidy screening with a cfDNA test should be aware of the possibility of this rare incidental finding. (See "Prenatal screening for common aneuploidies using cell-free DNA", section on 'False-positive cfDNA test results'.)
Vitamin D deficiency and risk for paclitaxel-related neuropathy (July 2022)
The predominant risk factor for paclitaxel-related peripheral sensory neuropathy (PSN) is cumulative dose over time; new data suggest that low vitamin D levels may contribute. In a retrospective analysis of data from the SWOG0221 trial comparing different paclitaxel-containing regimens for early-stage breast cancer, vitamin D levels ≤20 ng/mL were associated with a higher PSN risk (19.3 versus 13.0 percent) [66]. Compared with White American patients, more Black American patients had vitamin D deficiency (78 versus 29 percent) and more developed treatment-related PSN (29.3 versus 13.3 percent). Adjusting for vitamin D deficiency decreased but did not eliminate the higher PSN risk in Black American patients. Although prospective trials are needed to test whether vitamin D supplementation lessens paclitaxel-related PSN, these data suggest that patients initiating treatment with paclitaxel should be screened for vitamin D deficiency and repleted, if levels are low. (See "Overview of neurologic complications of conventional non-platinum cancer chemotherapy", section on 'Clinical features, incidence, and risk factors' and "Prevention and treatment of chemotherapy-induced peripheral neuropathy", section on 'Paclitaxel'.)
ASCO guideline on exercise and diet during cancer treatment (July 2022)
Previous guidelines from the American Society of Clinical Oncology (ASCO) for management of adult cancer survivors with fatigue recommended 150 minutes of moderate aerobic exercise (eg, fast walking, cycling, or swimming) per week, with an additional two to three strength training (eg, weight lifting) sessions weekly. A new guideline addressing the benefits of exercise and diet during active cancer treatment concluded that exercise leads to significant improvements in cardiorespiratory fitness, strength, and fatigue, moderate reduction in sleep disturbance, and a low frequency of adverse effects [67]. For patients with lung cancer, preoperative exercise may reduce hospital stay and the risk of postoperative complications. Oncology providers should recommend aerobic and resistance exercise during active, curative-intent cancer treatment and may recommend preoperative exercise for patients undergoing surgery for lung cancer. Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment. (See "Cancer-related fatigue: Treatment", section on 'Exercise' and "Overview of the initial treatment and prognosis of lung cancer", section on 'NSCLC'.)
Tissue-agnostic approval for dabrafenib plus trametinib in BRAF V600E-mutated tumors (June 2022)
Combined therapy with the BRAF and MEK inhibitors dabrafenib and trametinib has been granted a tissue-agnostic accelerated approval by the US Food and Drug Administration for the treatment of patients ≥6 years of age with unresectable or metastatic solid tumors harboring mutations in BRAF V600E following progression on previous treatment and with no satisfactory alternative treatment options [68]. Approval was based on data from the open-label phase II ROAR and NCI-MATCH trials that demonstrated objective response rates in a variety of refractory solid tumors with data from the open-label phase II ROAR and NCI-MATCH trials that demonstrated objective response rates in a variety of refractory solid tumors with V600E mutations, which were highest (up to 50 percent) in gliomas and biliary tract, gynecologic, and gastrointestinal (but not colorectal) tumors [69,70]. The most common adverse events in the NCI MATCH trial were fatigue, nausea, and fever and chills. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'BRAF V600E-mutated cancers'.)
