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PURPOSE: Patients with a cancer diagnosis have a high risk of re-admission during the 30 days after discharge. Clinicians, payers, and patients consider this to be an indicator of care quality. The causes of re-admission remain poorly understood. Retrospective chart reviews, used in most re-admission research, provide limited information regarding the causes of, and methods to reduce, re-admissions. This project sought to elicit the insights of those most affected by re-admission: the patients themselves. METHODS: We interviewed patients with cancer who were re-admitted to 2 urban teaching hospitals when they were hospitalized during their second admission. Trained interviewers used a semistructured interview guide to gather information on events just before the second admission, the patients’ understanding of the cause of re-admission, and the patients’ views about their readiness for discharge at the previous admission. Interviews were transcribed and analyzed, and themes were identified and explored. RESULTS: Three major themes were identified. First, most patients saw their re-admission as caused by problems that could not be treated in an outpatient setting. Second, the patients felt that they did not have sufficient resources at home to manage their care. Furthermore, the patients did not see the outpatient care team as a resource that they could call on for assistance. As a result, most of the decisions to return to the hospital were made by the patients themselves. CONCLUSION: The decision that leads to re-admission often happens at home, in response to unmanageable needs. Strengthening the bond between the care team and the patient, with the aim of providing care in the most appropriate setting, could decrease re-admissions in patients with cancer. Possible interventions include home visits, enhanced discharge planning, and telehealth services.

PURPOSE Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Introduction :The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent coronavirus-19 (COVID-19) pandemic has impacted hematologic malignancies (HM) care worldwide. Reported risk factors for severe COVID-19 presentation include older age, medical comorbidities, and cardiac disease - many of which apply to patients with HM (Guan et al., 2020; Zhou et al., 2020). Additionally, patients with HM may be at even higher risk of infections with or complications from SARS-CoV-2 due to immune dysfunction from their underlying disease or treatment (He et al., 2020). However, data regarding rates of infection and outcomes in this population are limited. Here we describe the demographic characteristics, coexisting conditions, presenting symptoms, treatment, and outcomes of a cohort of patients with HM and COVID-19 infection at network sites across the Sidney Kimmel Cancer Center- Jefferson Health. Methods : We created an HM-specific COVID-19 database within our health system. Patients were identified for inclusion in the database by physician referral and query of the electronic medical record. Epidemiological, clinical, and laboratory data, therapy details, and outcomes on patients were obtained by accessing electronic medical records. A retrospective study of patients with a diagnosis of a HM- within 5 years of COVID-19 diagnosis-and a confirmed diagnosis of COVID-19 were was conducted using this database. A confirmed diagnosis of COVID-19 was defined as a positive result on a real-time RT-PCR assay of a specimen collected by nasopharyngeal swab. Results: More than 3,000 telehealth or in-person patient visits were conducted for patients with HM in the Jefferson Health Network between March 9, 2020 and July 15, 2020. During that period, 21 patients with HM had a confirmed diagnosis of COVID-19. Median age was 67 years (range 21-89). The majority of patients (86%) had at least 1 comorbid medical condition, and 76% had a history of tobacco use. The most common HM was multiple myeloma (7/21, 33%), followed by diffuse large B-cell lymphoma (3/21, 14%). 12/21 (52%) patients were on active cancer treatment at the time of COVID-19 diagnosis, and patients had received a median of 2 lines of cancer therapy (range 0-6). All 12 patients who were on active therapy at the time of COVID-19 diagnosis experienced a treatment interruption. Two patients had undergone prior autologous stem cell transplant (SCT) and 1 had undergone prior allogeneic SCT. Details on HM diagnosis and treatment are presented in Table 1. Twenty patients required hospital admission at the time of COVID-19 diagnosis, 7/21 were admitted to the ICU, and 6/21 required intubation. The most common presenting symptoms were fever (48%), cough (43%), and shortness of breath (43%), and lymphopenia (absolute lymphocyte count (ALC) Conclusion : In contrast to published reports, we found that the number of confirmed COVID-19 in patients with HM at our center was surprisingly low, with only 21 cases in 4 months. Furthermore, the mortality rate of 14% was lower than expected when compared to published cohorts of similar patients, which have shown mortality rates as high as 40% (He et al., 2020; Malard et al., 2020; Martín-Moro et al., 2020). Postulated reasons for the low number of infections include the early adoption of universal masking and robust utilization of telehealth to promote social distancing. In our small cohort, multiple myeloma was the most frequent HM diagnosis associated with COVID-19 infection, but this may be related to the prevalence of MM in our geographic area. The vast majority of HM patients with symptomatic COVID-19 were former smokers. Disclosures Binder: Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy. Alpdogan:Seattle Genetics: Consultancy; Kiowa Kirin: Consultancy. Kasner:Otsuka Pharmaceutical: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Martinez-Outschoorn:Otsuka Pharmaceutical: Research Funding. Palmisiano:Genentech: Research Funding; AbbVie: Research Funding. Flomenberg:Tevogen: Consultancy, Honoraria. Porcu:Cell Medica: Research Funding; Daiichi: Consultancy, Honoraria; Galderma: Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kiowa Kirin: Research Funding; Kura Oncology: Research Funding; Miragen: Research Funding; Verastem: Consultancy; Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding.

Background: Chest wall recurrences represent a significant source of morbidity for breast cancer patients causing symptoms including bleeding, ulceration, infection and pain. Approximately 5 to 10% of breast cancer patients undergoing a mastectomy will have a chest wall or nodal recurrence within ten years after surgery. Loco-regional recurrence isolated to the chest wall occurs in 50 to 70% of these patients and only one third of these patients having synchronous metastases. After radiation, patients with unresectable isolated loco-regional breast cancer have very few treatment options. Hyperthermia, temperature elevation to 40° to 45°C for 60 minutes, is a potent radiotherapy and chemotherapy sensitizer without significant toxicity. Additionally, superficial hyperthermia can improve the complete response and local control in breast cancer patients with chest wall disease. Chest wall hyperthermia induces degradation of the BRCA2 protein, thereby leading to defective homologous recombination DNA repair, and sensitization to PARP-1 inhibitors. Krawczyk and colleagues (2017) showed that mild hyperthermia innately sensitizes homologous recombination proficient tumor cells to treatment with a PARP-1 inhibitor in pre-clinical models. Olaparib, is an oral targeted therapy that is an inhibitor of the poly ADP ribose polymerase (PARP) and is currently approved for treatment for patients with metastatic ovarian cancer and metastatic breast cancer with BRCA1 or BRCA2 mutation. Our hypothesis is that the combination of olaparib and chest wall hyperthermia will be a safe and tolerable combination for breast cancer patients with chest wall metastases. Trial Design: In this novel dose-escalation pilot trial, breast cancer patients with chest wall recurrences will be treated with olaparib at the appropriate dose level, concurrently with chest wall hyperthermia involving heating the skin to 43 ° Celsius for 1 hour. We plan to treat patients first with olaparib given twice a day in tablet form at the appropriate dose level for one week and then add hyperthermia twice a week for 3 weeks, for a total duration of 4 weeks of treatment. Eligibility criteria: Female breast cancer patients regardless of ER/PR/HER2 status who have chest wall recurrences greater than 2 cm are eligible for this study. Patients are eligible after any line of therapy and if they have wild-type germ-line BRCA1 or BRCA2 status. Specific Aims: We will evaluate the safety and determine the maximum tolerated dose of the combination of olaparib and chest wall hyperthermia. We will assess the local progression free survival, one-year progression free survival, overall response and quality of life scores for these patients. We plan to obtain skin biopsies to evaluate biomarkers of homologous recombination deficiency including BRCA1, BRCA2, RAD51 as well as γH2AX as an indicator of DNA damage. Statistical Methods: A 3+3 dose-escalation design will be used to determine the MTD of olaparib in combination with hyperthermia. We will initially enroll 3 subjects at each dose level. If one of the three experiences that level of toxicity, we will accrue 3 more subjects at that dose. If at any time there are two or more dose-limiting toxicities (in the 3-6 subjects) on a given dose, we will terminate accrual to the trial. No patient will be treated at a higher dose until the 3 or 6 patients have completed their 30 day toxicity evaluation period at the current dose. The survival endpoints of PFS and local PFS will be analyzed using log-rank test with Kaplan-Meier curves, as well as Cox proportional hazard models. Present Accrual and target accrual: Target accrual is 12 patients in the next two years. This study opened in May of 2019 at Thomas Jefferson University in Philadelphia, PA with full support from AstraZeneca. Clinical trial information: NCT03955640 Citation Format: Saveri Bhattacharya, Matthew Schiewer, Rita C. Murphy, Pramila Rani Anne, Nicole Simone, Voichita Bar Ad, Maysa Abu Khalaf, Daniel P. Silver, Rebecca Jaslow, Frederick M. Fellin, Allison M. Zibelli, Ana Maria Lopez, Adam Berger, Theodore N. Tsangaris, Melissa A. Lazar, Alliric I. Willis, Paul Stauffer, Mark D. Hurwitz. A pilot trial of hyperthermia in combination with olaparib in breast cancer patients with chest wall recurrences [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 OT2-03-02.

Inflammatory breast carcinoma (IBC) is the most aggressive form of breast cancer. The hallmark of IBC is regional extension into dermal lymphatics as tumor emboli causing breast edema and erythema. Pathologic characteristics of IBC include high grade, negative hormone receptor status and overexpression of HER2 and E-cadherin. The latter is the most attractive therapeutic target in IBC. In preclinical studies the histone deacetylase inhibitor, romidepsin targeted E-cadherin, affecting tumor emboli and increasing taxane sensitivity. Rationale: In vitro studies show that histone deacetylase inhibitors (HDACi) with taxanes provide synergy to enhance cell death. HDACi alter expression of AIRH1, a regulator of autophagy, typically silenced in breast cancer. In vitro treatment with HDACi induces expression of AIRH1, resulting in enhanced cell death with taxanes. In vitro studies of IBC have demonstrated the utility of HDACi and romidepsin in IBC cell lines. SAHA and romidespin, HDACis, inhibited self-renewal of IBC tumor spheroids from IBC cell lines. This trial combines romidepsin with a taxane proven in metastatic breast cancer to explore whether the combination will be effective in IBC. Design: This is a phase I trial to assess the safety of romidepsin plus nab-paclitaxel in patients with recurrent or metastatic IBC. The maximum tolerated dose (MTD) of romidepsin + weekly nab-paclitaxel was determined to define the dose for the phase II trial. Secondary objectives included describing the adverse event profile and assessing the overall response rate (ORR) and Clinical Benefit Rate (CBR). This study employed a 3+3 design. DLTs included febrile neutropenia or non-hematologic grade 3 or 4 toxicities. Patients were treated with nab-paclitaxel 100 mg/m2 iv with romidepsin, 7 mg/m2 iv (1st cohort) and 10 mg/m2 iv (2nd cohort), on days 1, 8, 15 of a 28 day cycle. Results: Nine patients were treated. The median age was 52. Three patients were treated in the first cohort. Two patients showed progressive disease (PD). One patient has had stable disease (SD) over 10 cycles and continues treatment. DLT was not reached at 7 mg. Toxicities related to romidepsin included neutropenia, anemia and fatigue. Six patients were treated in the 2nd cohort. Grade 3 hypophosphatemia, a DLT, was reached. One patient had complete response (CR). One patient had SD; four patients had PD. Toxicities related to romidepsin were anemia, neutropenia, GI upset, edema, hyperglycemia, fatigue, hypophosphatemia, pruritis, dry mouth, and increased lab values. The overall response rate (ORR) was 33% (3/9). The table below shows results. CohortResponse# Prior TherapiesMetastatic Sites# Cycles on study1PD2pleura, nodes51PD0lung31SD2lung, nodes102PD2pleura, nodes, soft tissue42PD0liver, nodes, bone22CR2 chemotherapy, 2 endocrinebone, nodes72SD0nodes52PD0lung,liver, nodes22PD0liver, bone, nodes2 Conclusions: This phase I trial shows that romidepsin and nab-paclitaxel are well-tolerated in patients with advanced IBC. The MTD and recommended dose of romidepsin is 10 mg/m2 with nab-paclitaxel 100 mg/ m2 days 1, 8, 15 of a 28 day cycle. A phase II trial is planned in recurrent HER negative IBC patients. Citation Format: Avery TP, Jaslow R, Basu-Mallick A, Zibelli A, Fellin F, Cristofanilli M. A phase I study of romidepsin in combination with nab-paclitaxel in patients with metastatic HER-2 negative inflammatory breast cancer (IBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-18.

e19118 Background: For patients being treated for solid tumor malignancies, an unplanned hospitalization is a significant event that may help predict outcomes. Prior studies have demonstrated a 1 year mortality rate as high as 73% for oncology patients following an unplanned admission. As our therapies continue to improve, better understanding of the significance of acute hospitalizations is needed to help influence management decisions for oncology providers. Methods: We conducted a retrospective review of all patients admitted to a solid oncology inpatient service at Thomas Jefferson University Hospital (TJUH) who were discharged between January 1st and March 31st 2019. We excluded all patients who had not established care with a provider at TJUH prior to the index admission. We collected data on age, sex, length of stay (LOS), diagnosis, treatment activity, ECOG performance status (PS), 30 day and total re-admissions, survival and whether hospice was discussed during index admission. We censored data at 180 days after date of index discharge. We evaluated overall survival (OS) using the Kaplan-Meier method and compared survival to 30-day readmission and ECOG status using a log-rank test. Results: During our investigational time period there were 263 discharges, which yielded a study population of 182 patients. Median LOS was 5 days and 55% of patients were female. Gastrointestinal and genitourinary cancers were the most prevalent, observed in 32% and 28% of patients respectively. 75% of patients were on active treatment at time of admission. Survival data was available in 174 patients and at 6 months, OS was found to be 47%. 35% of patients were readmitted within 30 days of their index discharge. Patients readmitted within 30 days had a significantly lower OS than patients without a readmission (31% vs. 56%, P = 0.002). 70% of patients had a PS of 0 or 1 prior to index admission and OS in this group was significantly better in comparison to patients with a higher ECOG score (57% vs. 33%, P = 0.001). Hospice was discussed with 31% patients during index admission. Conclusions: We observed a 6 month overall survival of 47% following an unplanned admission and this was lower for patients that were re-admitted within 30 days. Higher PS scores predicted worse outcomes; however, the majority of patients had a favorable PS prior to index admission. This study suggests that following an unplanned admission, oncology patients are at elevated risk for poor outcomes and that providers should reassess goals of care at follow up clinic visits.

Context : Postmastectomy pain syndrome is a common and debilitating complication of surgery of the breast or axilla. It is important for the clinician to understand how to recognize this syndrome and how to treat the pain and dysfunction that it causes. Evidence Acquisition : Studies were identified by searching PubMed for articles published from 1985 to 2017 using the terms “postmastectomy pain,” “complications of breast surgery,” “brachial plexopathy,” and “postoperative breast pain.” References from the relevant publications were searched. Articles were chosen based on relevance to the topic, quality of data, and publication in peer-reviewed journals. Results : Postmastectomy pain syndrome is underrecognized and underdiagnosed. There is no standard definition, but most authors recognize a syndrome of pain and dysfunction in the operated arm or anterior thorax that lasts from 3 months after surgery to indefinitely. Differential diagnosis includes neuroma, complex regional pain syndrome, axillary hematoma, axillary web syndrome, compressive radiculopathy, and brachial plexopathy. Possible treatment modalities include psychological support, physical therapy, TENS units, myofascial release, autologous fat grafting, venlafaxine, gabapentin, and capsaicin. Conclusions : Postmastectomy pain syndrome is a common entity that clinicians should recognize. Although there are multiple treatment options, more than one treatment may have to be tried to improve pain and dysfunction.

Purpose To report outcomes following adjuvant high-dose-rate vaginal brachytherapy (VBT) with or without chemotherapy for high-intermediate risk (HIR) and high-risk, early stage endometrial cancer as defined in Gynecologic Oncology Group trial 0249. Material and methods From May 2000 to January 2014, 68 women with HIR and high-risk endometrial cancer underwent surgical staging followed by VBT. Median VBT dose was 21 Gy delivered in three fractions prescribed to 0.5 cm depth. Paclitaxel 175 mg/m2 and carboplatin area under the curve 6 was administered every 21 days in sequence with VBT. Actuarial survival estimates were calculated using the Kaplan-Meier method. Results Patient demographics included a median age of 66 years (range: 36-91) and stages IA (49%), IB (38%), and II (13%), respectively. Thirty-one (46%) patients had HIR disease with endometrioid histology, and 33 (48%) patients had serous or clear cell histology. Thirty-seven (54%) patients received a median 3 cycles (range: 3-6) of chemotherapy in addition to VBT, and 65 patients (96%) completed all prescribed therapy. During a median follow up of 33.1 months (range: 4.0-161.7), four patients have recurred, including one vaginal recurrence. The 3-year estimates of vaginal, pelvic, and distant recurrences were 1.9%, 2.4%, and 9.1%, respectively. The 3-year rates of disease-free and overall survival were 87.7% and 93.9%, respectively. Conclusions Early outcomes with adjuvant VBT with or without chemotherapy demonstrate high rates of vaginal and pelvic control for women with HIR disease. Early vaginal and pelvic relapses in high-risk patients suggest that pelvic external beam radiotherapy is warranted in this subgroup, but additional data from large phase III trials is warranted.

Breast cancer is the most frequently diagnosed cancer in women. Developing breast cancers shed transformed cells into the blood. More malignant breast cancer cells appear in the blood at later stages. Early detection of circulating breast cancer cells might improve diagnosis of early breast cancer and ultimately might reduce deaths from breast cancer. We hypothesized that nanotube-antibody arrays could detect circulating human breast cancer cells in a drop of blood. Breast cancer cell surfaces show high levels of insulin-like growth factor 1 receptor (IGF1R), human epidermal growth factor receptor 1 (Her1, EGFR), and Her2 (Erb-B2, neu), among others. We have previously demonstrated antibody-specific nanodevice detection of ER+/Her2- MCF7 and ER+/Her2+ BT474 breast cancer cells suspended in a physiological buffer, and in fresh human blood. We discovered significant changes in conductance of single wall carbon nanotube-monoclonal antibody nanodevices upon exposure to human breast cancer cells in 2-5 microliter drops of physiological buffer or fresh donor blood. The nanodevices detected the cancer cells within 60 seconds and stabilized by five minutes. Control cells did not change nanodevice conductance. Breast cancer cells did not perturb the conductance of nanodevices with adsorbed anti-PSMA or nonspecific antibodies. Hence, the conductance change required a specific antigen-antibody complex between the live, intact breast cancer cell and the nanotube surface in blood. We postulate that sensing of breast cancer cell binding is due to cooperative stress on the surface of the nanotubes due to cellular binding to multiple antibodies. The stress on the nanotube is then thought to change its electron transport properties. Five microliter drops of blood from patients with metastatic breast cancer changed nanodevice conductance similarly to 10-100 MCF7 cells. Comparable circulating tumor cell numbers were obtained from 7.5 mL blood draws from the same patients analyzed by EpCAM bead capture and anti-cytokeratin staining. Single wall carbon nanotube-monoclonal antibody nanodevices provide the simplest and quickest method for direct detection of live cancer cells circulating in blood. Supported by a grant from the Breast Cancer Alliance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-72.

Novel developments in treatment have improved the 5-year survival rate for women diagnosed with epithelial ovarian cancer. In addition to standard surgical cytoreduction and platinum/taxane chemotherapy, bevacizumab has recently been demonstrated to improve the progression-free survival rate in patients with ovarian cancer (Burger et al., 2011). Bevacizumab is a humanized monoclonal antibody that binds to vascular endothelial growth factor A (VEGF-A), blocks the interaction with its receptor, and effectively alters angiogenesis (Braghiroli et al., 2012). Bevacizumab is thought to normalize hyperpermeable intratumoral blood vessels thereby increasing the delivery of simultaneously administered cytotoxic agents and, after continued treatment, collapsing these vessels (Martin and Schilder, 2007; Jain, 2005). Bevacizumab as a single agent has approximately a 20% response rate in recurrent ovarian cancer (Burger et al., 2007; Cannistra et al., 2007). This activity is among the highest for any cancer, and is probably because normal ovarian tissue is already primed to respond to VEGF for follicle maturation as well as growth and formation of the corpus luteum (Martin and Schilder, 2007). Although generally well tolerated, bevacizumab has a number of side effects including hypertension, arterial/venous thromboembolic events, proteinuria, neutropenia, gastrointestinal perforations, and, most important to this report, wound dehiscence (Braghiroli et al., 2012). The majority of wound-healing complications following bevacizumab have been reported early in the post-operative course, with few complications documented long after surgical intervention (Deshaies et al., 2010). To our knowledge, this is the first report of vaginal cuff evisceration at eight plus months post cytoreduction surgery for ovarian carcinoma soon after initiation of antiangiogenic therapy.