Abstract Background Clinical trials are an essential source for advances in oncologic care, yet the enrollment rate is only 2-4%. Patients' reluctance to participate is an important barrier. This study evaluates patients' level of understanding and attitudes towards clinical trials. Methods Two-hundred patients receiving active anti-neoplastic therapy at a large tertiary hospital completed an anonymous questionnaire comprised of demographic information, past experience in clinical research and basic knowledge on clinical trials. Results The majority of respondents did not meet the minimum knowledge level criteria. The concerns of those who replied that they would decline to participate in a clinical trial were related to assignment to the placebo arm, provision of informed consent and trust issues with their oncologist. Those with adequate knowledge were significantly more interested in participating in. Patients with past experience in clinical trials had a higher level of academic education, were less religious, had a better understanding of medical research and were inclined to participate in future research. Conclusions Misperceptions of clinical trials may contribute substantially to the unwillingness to participate in them. Trial registration The study was approved by the Tel Aviv Sourasky Medical Center ethics committee (0565-14-TLV January 7 th , 2015) and it was conducted in full accordance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Agreement to respond to the questionnaire was taken as formal consent to participate in this study.
Introduction: V600E BRAF mutation is an established driver mutation in a variety of tumors. Vemurafenib is a selective inhibitor of the BRAF V600E kinase, known to be highly effective in BRAF V600E-positive metastatic melanoma. As a single agent, vemurafenib is relatively ineffective in other V600E-positive malignancies.Case 1: A 72 year old man with metastatic CRC who failed several previous lines of chemotherapy. Genetic analysis of 315 cancer-related genes (Foundation Medicine, FMI) revealed a BRAF V600E mutation. The patient was treated with vemurafenib resulting in a partial response of 18 months. Genetic analysis following development of resistance revealed a new mutation in KRAS-G12R.Case 2: V600E mutation was identified in a 59 year old woman with metastatic PTC refractory to radioiodine therapy. The patient was treated with vemurafenib resulting in a partial response lasting 43 months. Genetic analysis following development of resistance revealed a new mutation in NRAS-Q61K.The presented cases demonstrated the development of rare RAS mutations as a genetic mechanism of acquired BRAF inhibitor resistance. This observation is strongly supported by the analysis of a large database consisting of 712 BRAF V600E-positive melanoma samples showing higher rates of BRAF V600E and RAS mutations co-occurrence in metastatic lesions compared to local tumors (OR = 3.8, p = 0.035). This enrichment is likely a result of the development of RAS mutations following treatment with BRAF inhibitors.Discussion: We report two cases showing extreme response to vemurafenib, which could not be predicted prior to treatment commencement. Genetic testing demonstrated a resistant mechanism not previously reported in CRC or PTC patients, namely an acquired mutation of RAS. This is supported by an analysis of a large cohort of BRAF V600E-positive melanomas.Further studies are needed in order to identify predictive markers for response to vemurafenib and to explore novel strategies to overcome RAS-mediated resistance.
Introduction: Rectal cancer is a common and lethal disease, with approximately 44,180 new cases of diagnosed annually in the United States and a five-year survival of 67% [1, 2]. The interval from diagnosis to chemoradiation treatment, or waiting time (WT), is considered to be an important quality indicator for cancer care and has been demonstrated to be associated with oncologic outcomes in various cancers [3, 4]. The current recommendation for pre-treatment staging evaluation includes rigid proctoscopy, PET CT, transrectal ultrasound (TRUS) and often rectal MRI. These diagnostic procedures may significantly postpone the start of treatment. We aim to examine the effect of WT on overall survival (OS) and disease free survival (DFS) of rectal cancer patients. Methods: Retrospective analysis was performed in a detailed database of patients with resectable primary rectal cancer who underwent chemoradiation between January 2000 and January 2019. Univariate and multivariate cox proportional hazard regressions were conducted in order to evaluate the effect of WT on oncological outcomes. Results: 387 patients were enrolled in our database; of them 297 patients were eligible by the inclusion criteria. Median WT was 6.3 weeks (IQR 4.3-8.7). Multivariate analysis showed adjusted Hazard Ratio (HR) for OS increases by 1.07 for each additional week of therapeutic delay in all age groups (p=0.025). Furthermore, focusing on the majority of patients in the age group 45 - 70 years, adjusted HR for OS increases by 1.12 for each additional week of therapeutic delay (p=0.011). Adjusted HR for DFS increases by 1.06 for each additional week of therapeutic delay in all age groups (p=0.045) and an increment by 1.09 for each additional week of therapeutic delay in age group 45-70 years (p=0.02). Conclusion: Prolonged WT leads to significant poorer overall survival in patients with primary rectal cancer who underwent chemoradiation and curative surgical treatment. This marks the importance of efficient diagnostic evaluation and clinical multidisciplinary decision making in a timeframe of 6 weeks in order to not jeopardize oncological outcomes.
e15537 Background: We evaluated real-life clinical experience with molecular profiling (MP)-guided therapy in metastatic gastric and oesophageal cancer in Israel Methods: This multicenter retrospective cohort study included patients with metastatic gastric or oesophageal cancer who were treated in the participating institutions and underwent MP (Caris Molecular Intelligence). Treatment was considered as having benefit if the ratio between the longest progression-free survival (PFS) post MP and the last PFS pre MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Results: The analysis included 46 patients (61% males; median age, 58 years; 57% with poorly-differentiated tumours). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified per patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy post MP (1-4 lines). In the 1 st -line post MP, 5 patients (18%) achieved partial response and 5 (18%) stable disease; the median (range) PFS was 4.3 (0.4-38.5) months. Twenty-four patients were evaluable for PFS ratio analysis; in 7 (29.2%), the ratio was ≥1.3. In one-sided exact binomial test vs. the null hypothesis, P = 0.019; therefore, the null hypothesis was rejected. Conclusions: Our findings demonstrated that implementing MP is feasible and that MP could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or oesophageal cancer.
The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dosage-limited oxaliplatin-related toxicity. To date, there are no successful interventions for CIPN prevention or treatment. A therapeutic role for cannabis in diabetic and HIV-related peripheral neuropathy and a protective role in CIPN have been suggested. We examined the effect of cannabis on oncologic patients with CIPN.Medical records of 768 consecutive patients treated with oxaliplatin and 5-fluorouracil-based combinations at a tertiary medical center from October 2015 to January 2018 were reviewed. Excluded patients were those with pre-existing neuropathy or patients who received fewer than two cycles of oxaliplatin treatment. CIPN grade, oxaliplatin cumulative dose, and neuropathy-free survival were evaluated. The patients were divided based upon the exposure to cannabis: prior to oxaliplatin (cannabis-first), cannabis following the initiation of oxaliplatin treatment (oxaliplatin-first), and no exposure (control).In total, 513 patients met the inclusion criteria, of whom 248 were treated with cannabis and 265 served as controls. The cannabis-first group included 116 (46.7%) patients and the oxaliplatin-first group included 132 (53.3%) patients. Demographic parameters were comparable between groups. There was a significant difference in CIPN grade 2-3 between cannabis-exposed patients and controls (15.3% and 27.9%, respectively, p < 0.001). The protective effect of cannabis was more pronounced among cannabis-first patients compared to oxaliplatin-first patients (75% and 46.2%, respectively, p < 0.001). The median oxaliplatin cumulative doses were higher in the cannabis-first versus the oxaliplatin-first versus the control groups (545 mg/m2, 340 mg/m2, and 425 mg/m2 respectively, p < 0.001).The rate of neuropathy was reduced among patients treated with cannabis and oxaliplatin. This reduction was more significant in patients who received cannabis prior to treatment with oxaliplatin, suggesting a protective effect. A large prospective trial is planned.
The use of telemedicine in oncology practice is rapidly expanding and is considered safe and cost effective. However, the implications of telemedicine on patient-physician interaction, patient satisfaction, and absence of the personal touch have not been studied to date. Following the spread of COVID-19, telemedicine services were rapidly incorporated at the Oncology Division of Tel Aviv Medical Center. We aimed to evaluate patients' perspectives and preferences regarding telemedicine and to assess whether this virtual communication platform affects the patient-physician relationship.Between March 2020 and May 2020, adult cancer patients who conducted at least one successful telemedicine meeting were interviewed by trained medical personnel. The interview was based on validated patient satisfaction questionnaires and focused on patient-physician interaction in relation to the last in-patient visit.Of 236 patients, 172 (74%) patients agreed to participate. The study population comprised mainly patients with gastrointestinal malignancies (n = 79, 46%) with a median age of 63 years (range 21-88). The majority of patients were male (n = 93, 54%). Eighty-nine (51.7%) patients were receiving active oncologic treatment, and 58 (33.7%) were under routine surveillance following completion of active therapy. Almost all had a sense of secured privacy (n = 171, 96%), the majority of patients affirmed that their concerns were met (n = 166, 93%) and perceived that eye contact with the treating physician was perceived (n = 156, 87%). Only a minority felt that the absence of physical clinic visits harmed their treatment (n = 36, 20%). Most patients (n = 146, 84.9%) wished to continue telemedicine services. A multivariate analysis revealed that higher satisfaction and visits for routine surveillance were both predictors of willingness to continue future telemedicine meetings over physical encounters (odds ratio [OR] = 2.41, p = .01; OR = 3.34, p = .03, respectively).Telemedicine is perceived as safe and effective, and patients did not feel that it compromised medical care or the patient-physician relationship. Integration of telemedicine is ideal for patients under surveillance after completion of active oncologic treatment. Physician communication skills workshops are warranted with implementing this platform.During the COVID-19 pandemic, telemedicine was rapidly implemented worldwide to facilitate continuity of quality care and treatment. Despite many potential setbacks, telemedicine has become a useful and safe tool for oncology practitioners to care for their patients. The use of telemedicine regarding patients' perspectives, emotions, and patient-physician communication in daily oncology practice has not been studied to date. This study demonstrated telemedicine is perceived as safe and effective and does not compromise medical care or the patient-physician relationship. Its use is ideal for surveillance after completion of active oncologic treatment. Physician communication skills workshops are warranted with implementing this platform.
e18898 Background: In Israel, the vast majority of cancer therapies are covered by a universal health insurance. We hypothesized that cancer poses a significant financial burden even in the presence of a comprehensive insurance. Methods: A survey was conducted among 233 actively treated cancer patients regarding their income, direct (i.e. medications, medical tests) and indirect expenses (i.e. transportation) and perception of financial burden. Income was stratified into three groups, low, average and high, as defined by the Israeli Statistical Bureau. Results: Median age of the patients was 63, 56% were women and 65% had metastatic disease. Low income was reported by 96 patients (41%) average by 62 patients (26%) and high by 75 patients (33%). As expected, less patients in the low income group had higher educations and more were religious and of non-Ashkenazi origin (p < 0.05 for all comparisons). Supplementary private health insurance was owned by 17%, 45% and 72% of the low, average and high income groups (p = 0.001). Surprisingly, all groups reported on similar out of pockets expenses on second opinion (~60% spent over 850 us$) and out of pocket drugs (~45% spent over 5500 us$), as well as on indirect expenses. The majority of the patients reported on significant financial burden, but this was more pronounced in the low income group (low 84%, average 65% and high 69%, p- 0.004). Despite similar expenses and similar utilization of private services, most patients in the low and average groups perceived their treatment as compromised compared to the high income group. Conclusions: Despite having comprehensive health insurance, most patients reported on out of pocket expenses on a wide array of non-evidence based services, and similar utilization was reported regardless of income. This has led to financial burden among most patients. These findings pose financial and ethical issues that should be considered by the oncologist as well as the ministry of health.
e18029 Background: Clinical trials are an essential part of the oncological care. However, literature indicates low accrual of only 2-4% of the oncologic population. One of the leading known barriers is the patient's hesitant attitude toward participation. This study aimed to evaluate the patients' population treated in the Tel Aviv Sourasky Medical Center (TASMC) oncology division and their understanding of clinical research in order to improve local recruitment strategies. Methods: An observatory, questionnaire based research was conducted. Patients receiving active oncology treatment in the TASMC oncologic day care unit were asked to complete an anonymous questionnaire, which was comprised of two main parts: the first evaluate demographic information and past experience in clinical research. The second investigated basic knowledge true/false test regarding clinical trials. The questionnaire was validated by both external and internal validity tests (α-Cronbach validity test) and was approved by the local ethics committee. Results: Two hundred patients completed the questionnaires. Median age was 60. 64% would consider participating in a clinical study. 23% (N = 46) had past experience in research, and compared to those with no experience they were found to have higher academic education (67.4% vs 36.9%, p < 0.0001), be more secular (76.1% vs 58.3, p = 0.037) and to have a better understanding of medical research (84.4%, vs 36.5%, p < 0.0001). They were also more inclined to participate in a future research (73% vs 44.9%, p = 0.01). Of those who would decline to participate and had failed the knowledge test (score less than 60%), the most frequent concern was related to the placebo arm (p = 0.055), ability to reject consent, and to trust issues with the treating oncologist. Conclusions: Despite a noteworthy readiness to enroll in clinical trials among the TASMC oncologic population, there were found significant knowledge and basic understanding gaps regarding clinical trials. Further efforts are needed to better understand specific accrual barriers and to develop an adapted information system.
