Background: Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events. Patients and Methods: A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability. Results: Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates—patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception—was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001). Conclusions: This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.
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J. Matt McCrary, David Goldstein, Terry Trinh, Hannah C. Timmins, Tiffany Li, Jasmine Menant, Michael Friedlander, Craig R. Lewis, Mark Hertzberg, Siobhan O’Neill, Tracy King, Annmarie Bosco, Michelle Harrison and Susanna B. Park
Michael Xiang and Elizabeth A. Kidd
Background: Cisplatin with definitive radiotherapy (RT) is considered the standard of care for cervical cancer; however, older women are frequently undertreated and have worse outcomes compared with younger patients. Because women aged ≥65 years have been disproportionately underrepresented in clinical trials, uncertainties exist regarding how much they benefit from the addition of cisplatin to RT. Patients and Methods: Women aged ≥65 years with nonmetastatic cervical cancer treated with definitive external-beam RT and brachytherapy were identified in the SEER-Medicare database. Death attributable to cervical cancer (cancer-specific mortality [CSM]) was evaluated against competing risks of death using Gray’s test. Propensity score analysis and the Fine-Gray multivariable regression model were used to adjust for baseline differences, including comorbidity. Results: The total cohort comprised 826 patients, of whom 531 (64%) received cisplatin, 233 (28%) were FIGO stage I, 374 (45%) were stage II, and 219 (27%) were stage III–IVA. Older age and chronic kidney disease significantly predicted omission of cisplatin. Virtually all cisplatin dosing was weekly, with a median of 5 cycles. Death from cervical cancer was significantly lower with cisplatin than without (5-year CSM, 31% vs 39%; P=.02; adjusted hazard ratio, 0.72; P=.02), which persisted in propensity score analysis. Receiving ≥5 cycles was required for benefit, as no difference in CSM was seen in patients receiving 1 to 4 cycles versus no cisplatin. Subgroup analyses revealed that the benefit of cisplatin persisted in women aged ≥75 years and those with early-stage disease. Incidence of cytopenia, nausea/vomiting, and hypovolemia increased in patients treated with cisplatin. Conclusions: Administration of cisplatin with definitive RT in women aged ≥65 years was associated with a significant benefit in the incidence of death attributable to cervical cancer, despite competing risks for mortality in an older population. Receiving at least 5 cycles of weekly cisplatin was required for benefit.
Ronan J. Kelly
Esophageal cancer has a poor prognosis, with 5-year survival rates ranging from 20% to 35% in the nonmetastatic setting. Despite advances in surgical techniques and optimization of chemoradiotherapy regimens, overall survival benefits have been incremental at best. Esophageal cancer requires a concerted multidisciplinary approach, perhaps more so than any other tumor type given the integral role played by the esophagus in maintaining calorific intake and the propensity for early spread through the lymphatics. This review describes the latest in surgical techniques to minimize postoperative complications and examines previous and ongoing systemic therapy approaches. Strategies that harness a patient’s own immune system hold great promise, and shifting checkpoint inhibitors from the metastatic setting to the neoadjuvant/adjuvant setting is currently being evaluated in phase II and III clinical trials. In addition, a much better understanding of the interplay between tumors and their immune microenvironment is clearly needed to better judge how best to engage each patient’s immune system, and there will be likely demonstrable differences between early-stage tumors and metastatic disease. This review highlights emerging data, which demonstrate that, in addition to The Cancer Genome Atlas classification of esophageal squamous cell carcinoma having a distinct molecular makeup compared with esophageal adenocarcinoma, there are also differing responses to PD-1 inhibitors. Histology and the underlying immune milieu may have important ramifications for the management of localized disease in the future, above and beyond PD-L1 expression, microsatellite instability status, and tumor mutational burden.
Zachary Veitch, Omar F. Khan, Derek Tilley, Patricia A. Tang, Domen Ribnikar, Douglas A. Stewart, Xanthoula Kostaras, Karen King and Sasha Lupichuk
Background: Reductions in adjuvant chemotherapy dose <85% for historical regimens (ie, cyclophosphamide/methotrexate/fluorouracil) are known to affect breast cancer survival. This threshold, in addition to early versus late dose reductions, are poorly defined for third-generation anthracycline/taxane-based chemotherapy. In patients with breast cancer receiving adjuvant 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-D), we evaluated the impact of chemotherapy total cumulative dose (TCD), and early (FEC) versus late (D only) dose reductions, on survival outcomes. Patients and Methods: Women with stage I–III, hormone receptor–positive/negative, HER2-negative breast cancer treated with adjuvant FEC-D chemotherapy from 2007 through 2014 in Alberta, Canada, were included. TCD for cycles 1 to 6 of <85% or ≥85% was calculated. Average cumulative dose was also calculated for early (cycles 1–3) and late (cycles 4–6) chemotherapy. Survival outcomes (disease-free survival [DFS] and overall survival [OS]) were estimated using Kaplan-Meier and multivariate analysis. Cohorts were evaluated for uniformity. Results: Characteristics were reasonably balanced for all cohorts. Overall, 1,302 patients were evaluated for dose reductions, with 16% being reduced <85% (n=202) relative to ≥85% (n=1,100; 84%). Patients who received TCD ≥85% relative to <85% had superior 5-year DFS (P=.025) and OS (P<.001) according to Kaplan-Meier analysis, which remained significant on univariate and multivariate analyses. In stratified late and early dose reduction cohorts, DFS and OS showed a significant inferior survival trend for dose reduction early in treatment administration in 5-year Kaplan-Meier (P=.002 and P<.001, respectively) and multivariate analyses (hazard ratio [HR], 1.46; P=.073, and HR, 1.77; P=.011, respectively). Dose delays of <14 or ≥14 days and granulocyte colony-stimulating factor use did not affect outcomes. Conclusions: Chemotherapy TCD <85% for adjuvant FEC-D affects breast cancer survival. Late reductions (D only) were not shown to adversely affect DFS or OS. Conversely, early reductions (FEC±D) negatively affected patient outcomes.
Prakash Manoharan, Ahmed Salem, Hitesh Mistry and Corinne Faivre-Finn
Elizabeth A. Nardi, Can-Lan Sun, Francisco Robert and Julie A. Wolfson
Background: In elderly patients with lung cancer, race/ethnicity is associated with not receiving treatment; however, little attention has been given to nonelderly patients (aged ≤65 years) with a range of disease stages and histologies. Nonelderly patients with lung cancer have superior survival at NCI-designated Comprehensive Cancer Centers (CCCs), although the reasons remain unknown. Patients and Methods: A retrospective cohort study was conducted in 9,877 patients newly diagnosed with small cell or non–small cell lung cancer (all stages) between ages 22 and 65 years and reported to the Los Angeles County Cancer Surveillance Program registry between 1998 and 2008. Multivariable logistic regression examined factors associated with nontreatment. Results: In multivariable analysis, race/ethnicity was associated with not receiving cancer treatment (black: odds ratio [OR], 1.22; P=.004; Hispanic: OR, 1.17; P=.04), adjusting for patient age, sex, disease stage, histology, diagnosis year, distance to treatment facility, type of facility (CCC vs non-CCC), and insurance status. With inclusion of socioeconomic status (SES) in the model, the effect of race/ethnicity was no longer significant (black: OR, 1.02; P=.80; Hispanic: OR, 1.00; P=1.00). Factors independently associated with nontreatment included low SES (OR range, 1.37–2.15; P<.001), lack of private insurance (public: OR, 1.71; P<.001; uninsured: OR, 1.30; P<.001), and treatment facility (non-CCC: OR, 3.22; P<.001). Conclusions: In nonelderly patients with lung cancer, SES was associated with nontreatment, mitigating the effect of race/ethnicity. Patients were also at higher odds of nontreatment if they did not have private insurance or received cancer care at a non-CCC facility. These findings highlight the importance of understanding how both patient-level factors (eg, SES, insurance status) and facility-level factors (eg, treatment facility) serve as barriers to treatment of nonelderly patients with lung cancer.
Featured Updates to the NCCN Guidelines
Deborah K. Armstrong, Ronald D. Alvarez, Jamie N. Bakkum-Gamez, Lisa Barroilhet, Kian Behbakht, Andrew Berchuck, Jonathan S. Berek, Lee-may Chen, Mihaela Cristea, Marie DeRosa, Adam C. ElNaggar, David M. Gershenson, Heidi J. Gray, Ardeshir Hakam, Angela Jain, Carolyn Johnston, Charles A. Leath III, Joyce Liu, Haider Mahdi, Daniela Matei, Michael McHale, Karen McLean, David M. O’Malley, Richard T. Penson, Sanja Percac-Lima, Elena Ratner, Steven W. Remmenga, Paul Sabbatini, Theresa L. Werner, Emese Zsiros, Jennifer L. Burns and Anita M. Engh
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.