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Clinical risk and Recurrence Score in hormone receptor-positive, HER2-negative breast cancer
Based on previous reporting from the TAILORx trial, a 21-gene assay called the Recurrence Score (RS) is used to provide prognostic information for those with hormone receptor-positive, HER2-negative breast cancer, and to predict benefit from adjuvant chemotherapy. However, whether combining clinical risk factors with the RS improves its predictive value is uncertain. In subsequent reporting of TAILORx, clinical-risk stratification, when used with the RS, provided further prognostic information for those with intermediate and high RS, and predicted benefit from chemotherapy in a subset of women <=50 years with intermediate scores [1]. We continue to use the RS in our decisions regarding adjuvant chemotherapy, and some contributors incorporate clinical risk factors for select women <=50 years with intermediate RS.
Duration of adjuvant oxaliplatin chemotherapy in high-risk stage II colon cancer
For patients with stage III (node-positive) disease who have earlier substages of disease (ie, T1-3N1), current data suggest that three months of adjuvant chemotherapy is noninferior to six months. However, whether three months of therapy with an oxaliplatin-containing adjuvant therapy for high-risk stage II (node-negative) colon cancer provides benefits equivalent to six months is less clear. In an analysis of data from four trials from the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration that included stage II disease, disease-free survival (DFS) was lower with three, compared with six, months of therapy (80.7 versus 84 percent) and a three-month course did not meet the threshold set for noninferiority [2]. However, toxicity rates, especially neurotoxicity, were lower with a three-month course. In our view, both three and six months of chemotherapy for patients with high-risk stage II colon cancer are now reasonable options, and the decision must be individualized, balancing the small absolute DFS benefit (3.3 percent) of a longer course with the increased risk of toxicity.
Lack of benefit for addition of pelvic radiation to chemotherapy in locally advanced endometrial cancer
Adjuvant chemotherapy is standard treatment for locally advanced endometrial cancer, but the role of adjuvant radiation is unclear. In a randomized trial (GOG-258) in over 700 patients with stage III to IVA endometrial cancer, the addition of pelvic radiation to chemotherapy did not improve relapse-free or overall survival [3]. While vaginal and pelvic and para-aortic nodal recurrences were less frequent among those assigned to pelvic radiation and chemotherapy, distant recurrences were more common. Given these and previous data, we suggest chemotherapy without pelvic radiation for most women with locally advanced endometrial cancer, although we add vaginal brachytherapy for some at high risk of relapse. We reserve pelvic radiation for those who are not candidates for chemotherapy.
Gemcitabine and cisplatin as induction chemotherapy in nasopharyngeal carcinoma
Induction chemotherapy prior to chemoradiation (CRT) in nasopharyngeal carcinoma (NPC) has been mainly reserved for tumor debulking prior to radiation therapy. Gemcitabine and cisplatin is an accepted regimen for recurrent or metastatic NPC, but until now its potential role as induction chemotherapy has not been established. In a randomized phase III trial of almost 500 patients with newly diagnosed locoregionally advanced NPC, the addition of induction chemotherapy with gemcitabine plus cisplatin to CRT improved three-year overall survival and was well tolerated, with similar rates of grade >=3 late toxicities [4]. This trial establishes the use of gemcitabine and cisplatin as an option for induction chemotherapy in patients with newly diagnosed NPC.
Long-acting opioid use and serious infection risk
Some opioids (morphine, methadone, fentanyl) have immunosuppressive properties in preclinical studies, and epidemiologic studies have linked opioid use to serious infection. In a population-based analysis of over 80,000 adult Tennessee Medicaid enrollees who were initiating long-acting opioids, hospitalization rates for serious infection were lower for patients initiating oxycodone, oxymorphone, or tramadol than for those initiating morphine, methadone, or fentanyl [5]. Among individual opioids, oxycodone users had a lower rate of infection than did morphine users. Additional studies are needed to confirm these observations and to determine whether risk varies with specific patient characteristics, different types of pathogens, and different opioids. Until then, it is reasonable for clinicians to consider an increased risk of serious infection as a potential adverse effect of opioids, which may be relatively higher with morphine, methadone or fentanyl.
1. Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med 2019; 380:2395.
2. Iveson T, Sobrero AF, Yoshino T, et al. Prospective pooled analysis of four randomized trials investigating duration of adjuvant (adj) oxaliplatin-based therapy (3 vs 6 months {m}) for patients (pts) with high-risk stage II colorectal cancer (CC) (abstract). J Clin Oncol 37, 2019 (suppl; abstr 3501). https://meetinglibrary.asco.org/record/171153/abstract (Accessed on June 11, 2019).
3. Matei D, Filiaci V, Randall ME, et al. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N Engl J Med 2019; 380:2317.
4. Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med 2019; May 31 (epub ahead of print).
5. Wiese AD, Griffin MR, Schaffner W, et al. Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study. Clin Infect Dis 2019; 68:1862.
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