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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating and dose-limiting side effect of neurotoxic chemotherapies that worsens quality of life and increases fall risk in cancer survivors. CIPN is painful and poorly managed with pharmacological agents.This pilot study assessed the preliminary effect of yoga on CIPN symptom severity and fall risk in cancer survivors.Methods: Breast and gynecological (GYN) cancer survivors with persistent, moderate-to-severe CIPN were randomized to yoga and usual care (UC) control arms. The yoga arm practiced Hatha yoga for 60 minutes daily via an in-person group class (2 times/week) and at home using a study-provided instructional video (5 times/week), and the UC arm received usual care for 8 weeks. Main study outcomes included a numeric rating scale (NRS) of CIPN pain, numbness and tingling (higher score indicates worse symptom); the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicitysubscale (FACT-GOG/Ntx) (higher score indicates improved symptoms); and functional reach (FR) test, an objective balance test used to evaluate fall risk (higher score indicates lower risk of fall). Mean changes from baseline to week 8 were calculated for each outcome measure and compared between treatment arms using two-sample t-tests. Results: From 2/2018 to 5/2019, 41 female cancer survivors (92.7% breast, 7.3% GYN; mean (SD) age 62.6 (10.2) years; 53.7% white/non-Hispanic, 19.5% African American, 12.2% Asian, 12.2% other) were enrolled and randomized to yoga (N=21) and UC (N=20) arms. At week 8, mean NRS pain decreased by 2.06 points (95% CI [-3.27, -0.86]) in the yoga arm, and 0.65 points [-2.08, 0.78] in the UC arm (p=0.12). No statistically significant change was observed in NRS numbness and tingling for yoga versus UC arms (both p>0.5). FACT-GOG/Ntx improved by 4.56 points [-1.84, 7.29] in the yoga arm, and 1.37 points [-0.51, 3.25] in the UC arm (p=0.05). FR improved by 3.08 inches [-1.43, 4.73] in the yoga arm, and decreased 0.59 inches [-0.51, 3.25] in the UC arm (p=0.003). Four yoga and 3 UC subjects reported a total of 11 adverse events deemed possibly related to the yoga intervention (all grade 1). Conclusion: Among breast and GYN cancer survivors with moderate-to-severe CIPN, yoga showed promising effects for improving neuropathy-related pain and quality of life, and for reducing fall risk. An adequately-powered and appropriately-controlled trial is warranted to confirm the specific and long-term effects of yoga on CIPN symptoms and fall prevention. Citation Format: Ting Bao, Madeline Hooper, Raymond Baser, Patricia Chen, Lauren Piulson, Clare Patterson, Tina Paul, Connie Chen, Qing Li, Katherine Panageas, Iris Zhi, Victoria Blinder, Mark Robson, Andrew Seidman, Jun Mao. Yoga for chemotherapy-induced peripheral neuropathy and fall risk in breast and gynecological cancer survivors: A pilot study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-02.

Background Leptomeningeal metastasis (LM) involves cerebrospinal fluid (CSF) seeding of tumor cells. Proton craniospinal irradiation (pCSI) is potentially effective for solid tumor LM. We evaluated whether circulating tumor cells (CTCs) in the CSF (CTCCSF), blood (CTCblood), and neuroimaging correlate with outcomes after pCSI for LM. Methods We describe a single-institution consecutive case series of 58 patients treated with pCSI for LM. Pre-pCSI CTCs, the change in CTC post-pCSI (Δ CTC), and MRIs were examined. Central nervous system progression-free survival (CNS-PFS) and overall survival (OS) from pCSI were determined using Kaplan Meier analysis, Cox proportional-hazards regression, time-dependent ROC analysis, and joint modeling of time-varying effects and survival outcomes. Results The median CNS-PFS and OS were 6 months (IQR: 4–9) and 8 months (IQR: 5–13), respectively. Pre-pCSI CTCCSF < 53/3mL was associated with improved CNS-PFS (12.0 vs 6.0 months, P < .01). Parenchymal brain metastases (n = 34, 59%) on pre-pCSI MRI showed worse OS (7.0 vs 13 months, P = .01). Through joint modeling, CTCCSF was significantly prognostic of CNS-PFS (P < .01) and OS (P < .01). A Δ CTC-CSF≥37 cells/3mL, the median Δ CTC-CSF at nadir, showed improved CNS-PFS (8.0 vs 5.0 months, P = .02) and further stratified patients into favorable and unfavorable subgroups (CNS-PFS 8.0 vs 4.0 months, P < .01). No associations with CTCblood were found. Conclusion We found the best survival observed in patients with low pre-pCSI CTCCSF and intermediate outcomes for patients with high pre-pCSI CTCCSF but large Δ CTC-CSF. These results favor additional studies incorporating pCSI and CTCCSF measurement earlier in the LM treatment paradigm.

To examine the toxicity experienced by a cohort of older women receiving adjuvant chemotherapy for breast cancer and the longitudinal effect on their functional status and quality of life (QOL).A geriatric assessment measuring functional status, comorbidity, mood, nutritional status, and QOL was performed before chemotherapy, at the end of chemotherapy, and 6 months later.This prospective longitudinal study was conducted at Memorial Sloan-Kettering Cancer Center, New York, New York.Fifty patients aged 65 and older with Stage I to III breast cancer receiving any adjuvant chemotherapy; 49 were evaluable.The chemotherapy regimen and the toxicity to chemotherapy were recorded. A geriatric assessment was performed before the start of chemotherapy, on completion of chemotherapy, and 6 months after completion of chemotherapy. QOL testing was performed at the same times.Patients (mean age 68, range 65-84) received an anthracycline-based chemotherapy regimen (n=15) or cyclophosphamide 600 mg/m2 intravenously (i.v.), methotrexate 40 mg/m2 i.v., 5-fluorouracil 600 mg/m2 i.v. every 3 weeks for eight cycles (n=34). Grade 3 or 4 toxicity occurred in 53% (n=26), hematological toxicity in 27% (n=13), and nonhematological toxicity in 31% (n=15). Despite toxicity, there was no significant longitudinal change in functional status or QOL.Despite toxicity from adjuvant chemotherapy, this cohort of relatively young older patients maintained their functional status and QOL from before chemotherapy to 6 months postchemotherapy. Subtle changes in higher-order functioning would require assessment using different geriatric assessment tools.

The need for accurate detection of HER2 status is becoming more apparent, as therapeutic decisions are influenced by this information in both the adjuvant and advanced-stage setting. Since the US Food and Drug Administration approved trastuzumab (Herceptin) for the treatment of metastatic breast cancer, the urgency of accurately evaluating HER2 status of breast cancer specimens, in order to identify patients who might benefit from this therapy, has increased. A wide range of assay methods are available for determining HER2 status, but immunohistochemistry followed by fluorescence in situ hybridization (FISH) is the recommended approach for ambiguous cases. FISH is not as widely available and is more costly than immunohistochemistry, but economic modeling shows that it is the most effective (and cost-effective) option.

Many factors contribute to patient survival in metastatic breast cancer and other late-stage cancers. It is doubtful that adjuvant therapy causes a worse survival outcome. This being said, should resistance develop following adjuvant therapy, the patient needs to be offered a first-line solution that is free of cross-resistance.