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Introduction: Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts.Methods: This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor. The Response Evaluation Criteria in Solid Tumors and response assessment in neuro-oncology brain metastases brain objective response rate (ORR) were evaluated by the in-vestigators. Median progression-free survival (mPFS), me-dian overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Muta-tions found at resistance were collected.Results: A total of 60 patients were included (22 centers, nine countries), with median age of 64 years, 75% females, and 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%), and de novo Thr790Met (T790M) (15%). The ORR was 61%, mPFS 9.5 months, mDOR 17.4 months, and median overall survival 24.5 months. Regarding patients with no concurrent common mutations or T790M (group A, n 1/4 44), ORR was 60%, mPFS 8.6 months, and mDOR 11 months. For G719X, ORR was 47%, mPFS 8.8 months, and mDOR 9.1 months. For L861Q, ORR was 80%, mPFS 16 months, and mDOR 16 months. For de novo T790M, ORR was 44%, mPFS 12.7 months, and mDOR 46.2 months. Compound EGFRmut including common muta-tions had better outcome compared with only ucEGFRmut. For 13 patients with a response assessment in neuro-oncology brain metastases-evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy results were analyzed: four patients with additional EGFR mutation (C797S, D585Y, E709K), three with new TP53 mutation, one with c -Met amplification, one with PIK3CA mutation, and one with neuroendocrine transformation. Conclusions: Osimertinib was found to have an activity in ucEGFRmut with a high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest data set of its kind.(c) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). No funding was provided to the participating centers. Centralized data collection, statistical analysis, and figure preparation were funded by AstraZeneca. The authors thank Ana Maria Iordan (MD, MSc) and Sorin Tita-Calin for excellent data management, statistical analyses, and figure preparation (MedInteractiv Plus [Bucharest, Romania; funded by AstraZeneca]). The authors also thank Judith Elbaz, Liesbet Lodewyckx, and Nathalie Sassi (AstraZeneca) for helpful discussions.

Treatment response assessment in patients with high-grade gliomas (HGG) is heavily dependent on changes in lesion size on MRI. However, in conventional MRI, treatment-related changes can appear as enhancing tissue, with similar presentation to that of active tumor tissue. We propose a model-free data-driven method for differentiation between these tissues, based on dynamic contrast-enhanced (DCE) MRI.The study included a total of 66 scans of patients with glioblastoma. Of these, 48 were acquired from 1 MRI vendor and 18 scans were acquired from a different MRI vendor and used as test data. Of the 48, 24 scans had biopsy results. Analysis included semi-automatic arterial input function (AIF) extraction, direct DCE pharmacokinetic-like feature extraction, and unsupervised clustering of the two tissue types. Validation was performed via (a) comparison to biopsy result (b) correlation to literature-based DCE curves for each tissue type, and (c) comparison to clinical outcome.Consistency between the model prediction and biopsy results was found in 20/24 cases. An average correlation of 82% for active tumor and 90% for treatment-related changes was found between the predicted component and population-based templates. An agreement between the predicted results and radiologist's assessment, based on RANO criteria, was found in 11/12 cases.The proposed method could serve as a non-invasive method for differentiation between lesion tissue and treatment-related changes.

Brain metastasis (BM) are uncommon among women with epithelial ovarian cancer (EOC). The frequency, risk factors and clinical repercussions of BM in these patients are not well described. We retrospectively evaluated EOC patients treated at our center from 2002 to 2020 and assessed their clinical parameters, risk for BM development and association with overall survival (OS). This cohort has a known high frequency of BRCA mutation carriers (BRCAm) due to women of Ashkenazi Jewish descent. Among 1035 EOC patients, 29 (2.8%) were diagnosed with BM. The prevalence of BRCA mutations was more common among women with BM (56.5% vs. 34.3%, p = 0.033). The BM rate in patients with BRCAm was higher than the BM rate in those with wildtype BRCA (BRCAw; 5.1% vs. 2.1%, OR = 2.6; 95% CI: 1.2–5.4, p = 0.013). Median time from diagnosis to BM and from disease recurrence to BM was longer among patients with BRCAm. Median OS was not significantly different among patients with BM versus those without BM (59.4 vs. 73.4 months, p = 0.243). After BM diagnosis, median OS was not statistically significantly different between patients with BRCAm and those with BRCAw (20.6 vs. 12.3 months, p = 0.441). Treatment with poly (ADP-ribose) polymerase inhibitors and bevacizumab had no impact on subsequent development of BM. BM are rare among EOC patients. However, the risk is three-fold higher among patients with BRCAm. BM do not significantly alter OS among EOC patients. The higher rate of BM in patients with BRCAm may be related to longer OS in this subpopulation.

662 Background: Upper abdominal / lower back pain characterizes celiac plexus involvement from pancreatic and other cancers which may impair HRQOL; its satisfactory treatment is an unmet clinical need. We hypothesized that ablative radiation delivered to the celiac plexus would decrease pain and improve HRQOL. Methods: An international single arm Phase II study included patients with an average pain level ≥ 5/11 on the brief pain inventory (BPI), ECOG 0-2, and anatomical involvement of the celiac axis. The intervention was a single fraction of 25Gy delivered to the celiac plexus. The primary endpoint was ‘complete or partial (≥2 points) pain response’ based upon the BPI ‘average pain’ 11-point scale. Changes in Health-related QOL at 3 & 6 weeks compared to baseline were secondary endpoints as measured by FACT-Hep, > 8 point change being the minimal clinically important difference (MCID). Evaluable patients included eligible irradiated subjects, who had stable pain levels pre-treatment, and were alive 3 weeks’ post-treatment. The sample size was 90 evaluable patients, giving 90% power to show response rate ≥ 40%. Opioid usage was assessed using intravenous morphine equivalent dose. Sensitivity HRQOL analyses imputed worsened outcomes (-9 for total FACT-Hep) for missing data. Results: Between 2018 and 2022, 149 patients were enrolled, 90/125 who received treatment were evaluable. Median age was 65.5 years (range 28-88), 65% were female, 92% had pancreatic cancer, and 86% had metastatic disease. Median Zubrod PS was 1, median number of systemic treatment lines was 1 (range 0-5), and median baseline opioid use 31 mg/d. At 3 weeks, 48 (53.3%, 95% CI 42.5-63.9) had at least a partial pain, the BPI ‘average pain’ score decreased by a mean of 2.5 points at 3 weeks (86/90 reported) and 3.2 points at 6 weeks (67/90 reported), both p < 0.001. Opioid usage decreased by 0.6 mg/d at 3 weeks (NS) and 16.9 mg/d at 6 weeks (p = 0.005). The FACT-Hep total score increased by 7.8 points at 3 weeks (54/90 reported, NS diff. from 8) and 16.6 points at 6 weeks (45/90 reported, sig. > 8, p = 0.01), showing an improvement in patients’ HRQOL. Changes in FACT-Hep were especially noted in the Physical Well Being subscale. The Trial Outcome Index (sum of physical, functional & disease-specific concerns) increased markedly at 3 weeks (6.6 points, p = 0.005) after treatment and even more after 6 weeks (14.5 points, p < 0.). Sensitivity analyses demonstrated improvements in HRQOL at 3 and 6 weeks (1.1, 3.8), but these were less than MCID. Conclusions: Celiac plexus SBRT decreases pain and opioid use amongst patients with pancreatic cancer and other tumors invading the celiac axis. The treatment appears to improve HRQOL. Supported by Gateway for Cancer Research and the Israel Cancer Association. Clinical trial information: NCT03323489 .

BACKGROUND Grade II and III meningiomas are invasive tumors which tend to recur following initial treatment and are associated with shorter survival (relative to grade I). Hemangiopericytoma (HPC) is a dural based tumor that originates in the pericytes. Treatment options for these tumors include surgical resection and radiation. There are no defined standard treatments after failure these modalities, and effective systemic treatments are lacking. This trial concept was developed following previous reports of high PD-L1 levels in anaplastic meningioma. We currently report our initial experience with pembrolizumab for refractory atypical/anaplastic meningioma (RAM) and HPC patients. METHODS This is a single arm, single institute, phase 2 trial. Inclusion criteria included patients with RAM or HPC whose all previous lines of treatment were exhausted. All patients were treated with pembrolizumab (200mg every 3 weeks) until disease progression. Primary endpoint was 6- and 12-months progression free survival (PFS). The study was planned for 25 patients and we report here preliminary results. RESULTS Through February 2021, 12 patients were enrolled to this study (two with HPC, 10 with RAM). After a median follow up of 18.5 months, the 6 and 12 months PFS were 25% and 16.7% respectively, with a median PFS of 2.75 months. Two patients had a partial response while all others progressed, making the overall response rate 16.7%. One of the responders had HPC and has been stable for 30 months, while the second had atypical meningioma and was stable for 13 months. Median survival has not been reached yet; 1 year survival rate was 82.5%. Grade 3 toxicities included hyperglycemia, elevated liver enzymes and fatigue, with no grade 4 or 5 toxicities. CONCLUSIONS Pembrolizumab induced a low response rate for RAM and HPC. However, a subset of patients might benefit from this treatment with a prolonged response period.

Background Brain metastasis (BM) are uncommon among ovarian cancer (OC) patients. Their frequency, risk factors and clinical repercussions are not well described. We assessed OC patients who developed BM, the role of BRCA status and survival implications. Methods Study cohort included OC patients treated at our center, from 2002–2020. We retrospectively evaluated clinical parameters, risk for BM development and association with survival data. Results Among 972 OC patients, 28 (2.9%) were diagnosed with BM. Comparing the BM to non-BM group, median age of 60 across both groups, stage III-IV at diagnosis was more common among BM group (96.4% vs. 84.8%, p=0.0065) while platinum sensitivity was similar (92.3% in BM vs. 80.8% in non-BM, p=0.2193). Out of 658 patients tested for BRCA, 33.6% (n=221) were BRCA mutation carriers (BRCA+). Of the patients with BM, 22 tested for BRCA, 13 were carriers. BRCA+ was significantly higher in the BM group compared to the non-BM group (59.1% vs. 32.9%, p=0.0123). Among BRCA+ the rate of BM was higher than among BRCA- (5.8% vs. 2.1%, p=0.0123, HR=3.029; 95%CI: 1.4–6.5). Median time from OC diagnosis to BM and from disease recurrence to BM, was longer for BRCA+ compared to BRCA- (44.3mo vs. 32.3mo and 11.8mo vs. 0.7mo, respectively). Median survival (mOS) was not significantly different among patients with BM compared to those without BM (59.4mo vs. 71.2mo, p=0.36). Following diagnosis of BM, mOS was 20.6mo among BRCA+ and 12.3mo among BRCA- (p=0.4266). No correlation was demonstrated with PARP inhibitors or bevacizumab treatment and subsequent development of BM. Conclusion BM are an infrequent event among OC patients. However, the risk is three-folds higher among BRCA+. Interestingly, BM do not significantly alter survival among OC patients. Our work suggests that the higher rate of BM in BRCA+ may be related to longer survival. Another hypothesis requiring further evaluation, is possible higher brain tropism among this population.

Background: TTFields are a loco-regional, anti-mitotic treatment comprising low-intensity alternating electric fields. In the EF-14 study of newly diagnosed glioblastoma (ndGBM), TTFields in combination with temozolomide (TMZ) significantly improved survival vs. TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This study prospectively evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) combined with daily TMZ (75 mg/m2). In the adjuvant phase, patients received monthly TMZ (150-200 mg/m2 for 5 days) plus TTFields. Patients were followed for 24 months or until second disease progression. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0. Results: Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and 80% patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1-2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure. Conclusions: Eighty percent of patients experienced grade 1-2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed without an increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Preliminary efficacy results are promising and warrant further investigation of concurrent TTFields/RT/TMZ treatment in ndGBM patients.

OBJECTIVES/HYPOTHESIS To assess the differences between patients with laryngeal squamous cell carcinoma under 40 years old and those 40 years old or older. A secondary objective was to compare survival outcome between these cohorts. STUDY DESIGN Retrospective chart review. METHODS We reviewed the medical charts of all patients treated in our tertiary referral center for laryngeal squamous cell carcinoma from 2005 to 2014. Patients aged

Introduction: Due to the neurocognitive side effects of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing frequency. The use of SRS is expanding for patients with multiple (>4) brain metastases (BM). This study summarizes our institutional experience with single-fraction, linear-accelerator-based SRS for multiple BM. Methods and materials: All patients who were treated between January 1, 2013, and September 30, 2015, with single-fraction SRS for ≥4 BM were included in this institutional review board–approved, retrospective, single-institution study. Patients were treated with linear accelerator–based image guided SRS. Results: A total of 59 patients with ≥4 BM were treated with single-fraction SRS. The median follow-up was 15.2 months, and the median overall survival for the entire cohort was 5.8 months. The median number of treated lesions per patient was 5 (range, 4-23). Per patient, the median planning target volume (PTV) was 4.8 cc (range, 0.7-28.8 cc). The prescribed dose across all 380 BM for the 59 patients ranged from 7 to 20 Gy. The median of the mean dose to the total PTV was 19.5 Gy. Although the number of treated lesions (4-5 vs ≥6) did not influence survival, better survival was noted for a total PTV 12 Gy to ≥10 cc of normal brain had worse survival (5.1 vs 8.6 months, respectively; P = .0028). Conclusion: In single-fraction SRS for patients with multiple BM, smaller total tumor volume, higher total dose, and lower volume of normal brain receiving >12 Gy were associated with increased survival. These data suggest that using SRS for the treatment of multiple BM is efficacious and that outcomes may be affected more by total tumor volume than by the number of lesions.

The objective of this study was to review and assess the impact of additional induction chemotherapy to concomitant chemoradiation in head and neck squamous cell cancer. We performed a comparative systematic review and meta-analysis of clinical trials of induction chemotherapy + chemoradiation and chemoradiation alone in this setting. We identified trials randomizing 1314 patients (published 2004-2015). A non-statistically significant trend was observed in favor of induction chemotherapy + chemoradiation on overall survival (hazard ratio, 0.88; 95% confidence interval, 0.75-1.04). Disease control was superior in the induction chemotherapy + chemoradiation group (hazard ratio, 0.69; 95% confidence interval, 0.57-0.83). The rate of complete response improved with induction chemotherapy compared with concomitant chemoradiation (relative risk, 1.52; 95% confidence interval, 1.20-1.92). This study showed no benefit of induction chemotherapy + chemoradiation on overall survival. However, improved complete response rate and death certificate-only registrations may imply that selected patients may benefit from induction chemotherapy.

Managing relapsing metastatic, head and neck squamous cell carcinoma (HNSCC) is challenging. The genomic landscape of HNSCC has been recently described by numerous studies, however clinical utility studies are absent...

Background The optimal treatment for locally advanced laryngeal cancer remains controversial. The purpose of this trial was to determine if the response to induction chemotherapy could select patients for organ preservation protocols, and improve larynx-preservation rates without compromising overall survival (OS). Methods The cohort comprised 12 patients with T3 disease and 14 with T4. Induction chemotherapy consisted of docetaxel, cisplatin, and 5-fluorouracil (TPF). Response to the first cycle was determined by examination and positron emission tomography (PET)-CT. Responders (>50% tumor reduction) underwent chemoradiation, whereas nonresponders underwent laryngectomy. Results Eighty-three percent of the patients had a response and 17% had stable or progressive disease. At 2 years, the median OS was 80%, the larynx-preservation rate was 83%, and the disease-specific survival rate was 86%. Response to a single TPF cycle was associated with 2-year OS (92% vs 50%; p = .02). The T classification was not predictive of survival. Conclusion Response to a single TPF-based cycle may identify patients with advanced laryngeal cancer who are amenable to organ preservation treatment. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Background Treatment for early-stage tongue squamous cell carcinoma (SCC) is usually surgery alone. There is ambiguity regarding the impact of minor adverse features (MAFs) on outcome and the role of postoperative radiotherapy (PORT) in tongue SCC. Methods A retrospective analysis was performed on 48 patients diagnosed with tongue SCC treated in our center. Patients with MAFs received adjuvant PORT. Disease outcome in patients with MAFs, and the effect of PORT were analyzed using the Kaplan–Meier method and log-rank test. Results Thirty-one patients had T1 and 17 had T2 disease. PORT was given to 7 patients with MAFs. Mean follow-up time was 70 months. The 2-year overall survival (OS) rate was 86%. Perineural invasion had a significant impact on disease-free survival (DFS; p =.05). There was an improved DFS in patients with MAFs treated with PORT (p =.01). Conclusion MAFs may have an impact on outcome in tongue SCC, and PORT can improve disease outcome in these patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 147–150, 2017

Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

Objectives/Hypothesis Despite advances in radiotherapy and chemotherapy treatments for head and neck cancers, the local failure rate is high. In most radiotherapy-resistant cases, surgery is performed; however, some cases are considered unresectable. No standard treatment for these situations has been established. In this study, we review our experience with brachytherapy (BT), which has a different biological mechanism than standard radiotherapy. Methods All patients received prior radiation to the recurrence area. Median high-dose radiation BT dose was 50 Gy, administered in 5 to 10 Gy fractions twice daily for 5 days. High-dose radiation was given via four to 10 catheters inserted under local anesthesia (3 patients) or general anesthesia with preventive tracheostomy (10 patients). Results Thirteen patients received BT from 2010 to 2014. Male:female ratio was 1.6:1, and median age was 66 years (range 23–89). Of those 13 patients, 10 patients were diagnosed with squamous cell carcinoma (SCC) of the oral cavity, two patients with SCC of the nasal mucosa, and one patient with eccrine duct carcinoma. Prior radiation dose ranged from 60 to 70 Gy. Local control was achieved in 11 of 13 patients; only 15.3% (2 of 13) had in-field recurrence. Five patients developed local out-of-field recurrence, and two developed distant metastases. Five patients are alive with no evidence of disease. No major toxicities were encountered. Two patients had severe mucositis and recovered within several weeks. Conclusion Brachytherapy for radiotherapy-resistant head and neck cancers is feasible with minor adverse events, which enables good local control. However, many advanced head and neck cancers develop regional or distant metastases; therefore, additional treatment should be suggested. Level of Evidence 4. Laryngoscope, 2016

OBJECTIVE In the EF-14 phase 3 trial, TTFields 9200 kHz) added to maintenance TMZ increased median OS to 20.9 months versus 16.0 months with maintenance TMZ (p< 0.001) in ndGBM. Preclinical investigations showed that TTFields/RT have a synergistic effect. A pilot study (N=10) in ndGBM demonstrated the feasibility and safety of TTFields combined with RT/TMZ (Grossman Front Onc 2020). The only TTFields-related adverse event was array-associated skin toxicity. Median PFS was 8.9 months. Based on these encouraging results, this prospective, randomized phase 2 study [NCT03869242] in 60 patients further investigates if the addition of TTFields TMZ/RT treatment in ndGBM patients improves treatment efficacy and delays disease progression. METHODS Following debulking surgery or biopsy, 60 patients (≥18 years) with histologically confirmed GBM, KPS≥70 and life expectancy >3 months will be randomized 1:1 to: i) RT with concomitant TMZ/TTFields (200 kHz) for 6 weeks followed by up to 6 months of maintenance TMZ combined with TTFields (experimental arm) up to 24 months; or ii) RT with concomitant TMZ alone followed by maintenance TMZ combined with TTFields (control arm). Patients with early progressive disease, significant comorbidities precluding maintenance RT or TMZ or with implanted electronic devices will be excluded. The primary endpoint is the rate of progression free survival at 12 months (PFS12). Treatment with TTF will be continued until second progression or 24 months (the earlier of the two). All patients will be followed for survival. All adverse events will graded per CTCAE V5.0. The sample size of 60 patients provides 80% power with two-sided alpha level of 0.05 to detect a PFS12 of 46.5% with RT/TMZ/TTFields compared to 29.4% with RT/TMZ followed, respectively, by maintenance TMZ/TTFields (calculated from the RT/TMZ followed by maintenance TMZ/TTFields arm of the EF-14 trial). Follow-up will continue for >12 months from recruitment of the last patient.

Background: Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment comprising low-intensity alternating electric fields. In the phase III EF-14 study in newly diagnosed glioblastoma (ndGBM), TTFields in combination with temozolomide (TMZ) significantly improved survival compared with TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This pilot study [NCT03780569] evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) in combination with daily TMZ (75 mg/m2). In the adjuvant phase, patients received monthly TMZ (150-200 mg/m2 for 5 days) plus TTFields. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0. Results: Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and eight (80%) patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1-2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure. Conclusions: Eighty percent of patients experienced grade 1-2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed and there was no increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Based on the safety and preliminary efficacy results of this pilot study, a phase 2 randomized trial (N=60; NCT03869242) and the Phase 3 TRIDENT trial have been initiated to further investigate the efficacy of concomitant RT/TMZ/TTFields in ndGBM. Citation Format: Felix Bokstein, Deborah Blumenthal, Dror Limon, Carmit Ben Harosh, Zvi Ram, Rachel Grossman. Concurrent Tumor Treating Fields (TTFields) and radiation therapy for newly diagnosed glioblastoma: A safety and feasibility study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT206.

e14535 Background: Tumor Treating Fields (TTFields), a non-invasive, loco-regional, anti-mitotic treatment comprises low-intensity alternating electric fields. In the phase III EF-14 study in newly diagnosed glioblastoma (ndGBM), TTFields in combination with temozolomide (TMZ) significantly improved survival compared to TMZ alone. In preclinical studies TTFields had a radiosensitizing effect and increased the efficacy of radiation therapy (RT). This pilot study [NCT03780569] evaluated the feasibility and safety of TTFields administered concurrently with RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by adjuvant TMZ/TTFields. TTFields (200 kHz) were delivered for ≥18 hours/day with transducer arrays removed during RT delivery. RT was administered to the tumor bed in 30 fractions (total dose 60 Gy) in combination with daily TMZ (75 mg/m2). In the adjuvant phase, patients received monthly TMZ (150–200 mg/m2 for 5 days) plus TTFields. The primary outcome was safety of the combined therapies; secondary outcomes included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were graded per CTCAE v4.0. Results: Ten patients were enrolled at a single center between April and December 2017. Median age was 60.2 years, median Karnofsky Performance Score was 90.0, and eight (80%) patients were male. Five (50%) patients had undergone tumor resection while the remainder had biopsy only. Eight patients experienced ≥1 RT treatment delay; delays were unrelated to TTFields treatment. All patients experienced ≥1 AE. Three patients suffered from serious AEs (urinary tract infection, confusional state, and decubitus ulcer) that were considered unrelated to TTFields. The most common AE was skin toxicity, reported in eight (80%) patients; all were of low severity (CTCAE grade 1–2) and were reported as related to TTFields treatment. Median PFS from enrollment was 8.9 months; median OS was not reached at the time of study closure. Conclusions: Eighty percent of patients experienced grade 1–2 TTFields-related skin toxicity. No other TTFields-related toxicities were observed and there was no increase in RT- or TMZ-related toxicities as a result of combining TTFields with these therapies. Based on the safety and preliminary efficacy results of this pilot study, a phase 2 randomized trial (N = 60; NCT03869242) and the Phase 3 TRIDENT trial have been initiated to further investigate the efficacy of concomitant RT/TMZ/TTFields in ndGBM. Clinical trial information: NCT03780569.

We report on a series of nine patients with high grade glioma (HGG) who developed punctate contrast-enhancing foci on MRI, several years after tumor treatment. The lesions were considered suspicious for tumor progression at their onset, but were proven over time to be benign in nature. Five of the patients were treated for glioblastoma; 3 for anaplastic astrocytoma, and one for anaplastic oligodendroglioma. Median age of the patients at diagnosis was 48 years (31–62 years). The mean time of onset of “suspicious spots” following treatment was 51 months after diagnosis (6–170 months). Of note, median overall survival of the group is 96 months; with none of the nine patients deceased, and only 2 patients known to have progression. The remainder of the 7 patients are free of active tumor and being followed off treatment. No apparent clinical manifestations of the lesions have been observed. The majority of the punctate lesions were of a dynamic nature; they appeared and spontaneously disappeared over time, without intervention. All lesions developed within the field of radiation treatment; some were contralateral to the tumor. Radiological characteristics of the lesions including analysis of SWI, DWI, and DCE magnetic resonance imaging sequences will be reported. Punctate enhancing foci in the region of radiation treatment are phenomena which may be manifestation of delayed treatment sequelae in HGG. Patients with these lesions are on average of younger age and have a particularly long survival. These lesions appeared several years following oncological treatment. The foci should be initially followed more closely until shown to be of a non-progressive nature; they should not be presumed to be indicative of tumor recurrence. Possible etiology of the lesions may be related to vascular changes induced by radiation.

BACKGROUND: Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment comprising low intensity alternating electric fields. In the phase 3 EF14 study in newly diagnosed glioblastoma (ndGBM), TTFields/temozolomide significantly improved survival versus temozolomide alone. TTFields increased glioma cells undergoing cellular death following radiotherapy (RT), suggesting a radiosensitizing effect that enhances RT efficacy. This single center study is the first to investigate TTFields concomitant to RT in ndGBM. METHODS: Enrolled ndGBM patients (N=10), KPS 70 had recovered from maximal debulking surgery or biopsy. Patients started TTFields prior to or at the time of RT, and were on stable/ decreasing corticosteroids doses for 7 days pre-enrollment. Patients received TTFields (200 kHz; 18 hours/day) with daily removal of transducer arrays during RT, temozolomide (75 mg/m2/daily for 6 weeks) and 60 Gy RT. Endpoints included safety of TTFields/RT (primary) and preliminary efficacy. RESULTS: Patients were 59 years (42–71), KPS 90 (80–100) and mostly male (80%). Five patients (50%) underwent gross total resection while rest had biopsy only. Median dose of RT was 60 Gy (range 52–60 Gy). Six patients (60%) reported have an adverse event (AE) to-date. The most common AE was TTFields-related skin toxicity in 4 (40%) patients; none were severe. All other AEs reported occurred in only one patient and be attributed to underlying disease or chemotherapy. Two reported serious AEs (seizures and general deterioration) were considered unrelated to TTFields. Median PFS was 10.5 months (95%CI 2.67–10.5). PFS rate at 6 months was 80% (95%CI 40.9–91.6). CONCLUSION: The proportion of TTFields-related skin toxicity (40%) was similar to that reported in phase III study (52%), where patients started TTFields > 4 weeks after RT. No other TTFields-related toxicities were reported, nor was there an increase in RT- or temozolomide-related toxicities from combining TTFields with these therapies. Preliminary survival data are encouraging.

The increased survival of patients with gastroesophageal adenocarcinoma (GAD) following improvements in treatment has been accompanied by a rising incidence of secondary brain metastasis. HER2 amplification/overexpression, which has been associated with an increased risk of brain metastasis in breast cancer, is found in about 20% of patients with GAD. The aim of this study was to evaluate the effect of HER2 status on brain metastasis in GAD. The database of a tertiary cancer center was searched for patients with GAD diagnosed in 2011–2015, and data were collected on clinical characteristics, brain metastasis, HER2 status, and outcome. We identified 404 patients with a confirmed diagnosis of GAD. HER2 results were available for 298: 69 (23.2%) positive and 227 negative. Brain metastasis developed in 15 patients with GAD (3.7%); HER2 results, available in 13, were positive in 6, negative in 6, and equivocal in 1. The brain metastasis rate was significantly higher in HER2-positive than HER2-negative patients with GAD (6/69, 8.7% vs. 6/227, 2.6%; RR = 3.3, 95% CI 1.1–9.9, p = 0.034). Median overall survival from diagnosis of brain metastasis was 2.3 months, with no significant difference by HER2 status. HER2 positive GAD patients may be at increased risk to develop BM. Clinicians should maintain a lower threshold for performing brain imaging in patients with HER2-positive GAD given their increased risk of brain metastasis. The role of anti-HER2 agents in the development and treatment of brain metastasis in GAD warrants further study.

Neuro-oncology is a subspecialty attracting physicians from medical disciplines such as neurology, neurosurgery, pediatrics, oncology, and radiotherapy. It deals with diagnosis and management of primary brain tumors, as well as metastatic and non-metastatic neurological manifestations that frequently affect cancer patients including brain metastases, paraneoplastic syndromes and neurological complications of cancer treatment. A neuro-oncology unit was established in Davidoff Cancer Center at Rabin Medical Center. It provides a multidisciplinary team approach for management of brain tumors and services, such as expert outpatient clinics and inpatient consultations for the departments of oncology, hematology, bone marrow transplantation and other departments in the Rabin Medical Center. In addition, expert consultation is frequently provided to other hospitals that treat cancer patients with neurological manifestations. The medical disciplines that closely collaborate for the daily management of neuro-oncology patients include radiotherapy, hematology, oncology, neuro-surgery, neuro-radiology and neuro-pathology. The neuro-oncology center is also involved in clinical and laboratory research conducted in collaboration with researchers in Israel and abroad. The new service contributes substantially to the improved care of cancer patients and to the advance of research topics in the field of neuro-oncology.

To assess the differences between patients with laryngeal squamous cell carcinoma under 40 years old and those 40 years old or older. A secondary objective was to compare survival outcome between these cohorts.Retrospective chart review.We reviewed the medical charts of all patients treated in our tertiary referral center for laryngeal squamous cell carcinoma from 2005 to 2014. Patients aged 40 years at diagnosis were compared to older patients.The study group comprised 160 patients. Of them, 13 were aged 40 years at diagnosis. Mean age was 35 ± 3.9 years and 64.4 ± 11 years for the two groups. Among the younger patients, 38% were smokers (mean pack/day, 2.2) versus 71% in the older group (mean pack/day, 3). The younger group typically had a more advanced stage than the older group at presentation; eight young patients (62%) had stage III or IV versus 49 (33%) in the older group (P = .042). Mean overall survival was 6.7 ± 1 years for those under 40 years old and 7.7 ± 0.2 years for the older patients (P = .2). The 5-year survival rate was 69% for young patients and 90% for the older group (P = .04). However, there was no significant between-group difference in overall survival or 5-year survival rate when stratified for early- and late-stage disease.There is a lower prevalence of classic risk factors in younger patient with laryngeal carcinoma in this study, suggesting a different etiology compared to our older cohort. The under-40 cohort presented with more advanced disease and had a worse 5-year survival; however, when stratified for early- versus late-stage disease, there was no significant difference in overall or 5-year survival between the groups. This may suggest that, despite a different etiology, laryngeal cancer behaves similarly in older and younger patients.4. Laryngoscope, 128:1602-1605, 2018.

Late complications of cerebral radiation therapy (RT) involve vascular injury with acquired cavernous malformation, telangiectasias and damage to vascular walls which are well recognized in children. Its incidence in adults is unknown. Blood products and iron deposition that accompany vascular injury create paramagnetic effects on MRI. This study retrospectively investigated the frequency of paramagnetic lesions on routine surveillance MRI of adult brain tumor patients. MRI studies of 115 brain tumor patients were reviewed. Only studies containing sequences of either susceptibility weighted images or gradient echo or blood oxygenation level dependent imaging were included. Lesions inside the tumor volume were not considered. 68 studies fulfilled the above criteria and included 48 patients with previous RT (35 followed for >2 years and 13 for 1 year) and 20 patients who were not treated with RT. The median age at time of irradiation was 47 years. Aberrant paramagnetic lesions were found in 23/35 (65%) patients followed for >2 years after RT and in only 1/13 (8%) patients followed for 1-year after radiation (p = 0.03). The 1-year follow-up group did not differ from the control group [2/20 (9%)]. Most lesions were within the radiation field and none of the patients had related symptomatology. The number and incidence of these lesions increased with time and amounted to 75% over 3 years post RT. MRI paramagnetic signal aberrations are common findings in adult brain tumor patients that evolve over time after RT. The clinical significance of these lesions needs further investigation.

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients.One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist.Histological validation confirmed that regions of contrast agent clearance in the TRAMs1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P.0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated.The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

Background: Despite attempts to improve the outcome of patients with glioblastoma (GBM), the 3-year survival of patients treated with maximal surgical resection, radiation therapy (RT) and temozolomide (TMZ), followed by maintenance TMZ for 6 months is only 6% with a median OS of 14.6 months. In the EF-14 Phase III trial, the addition of Tumor treating fields (TTFields) at 200 kHz to maintenance TMZ increased the median OS to 20.9 months, compared with 16.0 months with maintenance TMZ alone (HR, 0.63; 95% CI, 0.53-0.76; p Methods: Following debulking surgery or biopsy, 60 adult patients (≥18 years) with histologically confirmed GBM, KPS≥70 and life expectancy of at least 3 months will be randomized 1:1 to either i) RT with concomitant TMZ and TTFields (200 kHz) for 6 weeks followed by up to 6 months of maintenance TMZ in combination with TTFields (experimental arm) up to 24 months; or ii) RT with concomitant TMZ alone followed by maintenance TMZ in combination with TTFields (control arm). Patients with early progressive disease, significant comorbidities precluding maintenance RT or TMZ or patients with an implanted electronic device will be excluded. The primary endpoint is the rate of progression free survival at 12 months (PFS12). Treatment with TTF will be continued until second progression or 24 months (the earlier of the two). All patients will be followed for survival. Grading and severity of all adverse events will be recorded using CTCAE V5.0. The sample size of 60 patients provides 80% power with a two-sided alpha level of 0.05 to detect a PFS12 of 46.5% with RT/TMZ/TTFields compared to 29.4% with RT/TMZ followed, respectively, by maintenance TMZ/TTFields (calculated from the RT/TMZ followed by maintenance TMZ/TTFields arm of the EF-14 trial). It is forecasted to take 24 months to fully recruit. Follow-up will continue for >12 months from recruitment of the last patient. Citation Format: Rachel Grossman, Dror Limon, Felix Bokstein, Carmit Ben Harosh, Zvi Ram. Randomized Phase II trial of Tumor Treating Fields plus radiation therapy plus temozolamide compared to radiation therapy plus temozolomide in patients with newly diagnosed glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT203.

Background: Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment comprising low intensity alternating electric fields. In the Phase III EF-14 study in newly diagnosed glioblastoma (ndGBM), TTFields significantly improved survival compared to temozolomide (TMZ). Preclinical data have demonstrated that TTFields increased glioma cell death following radiation therapy (RT), suggesting a radio-sensitizing effect of TTFields. We therefore initiated a pilot study to evaluate the safety and feasibility of administering TTFields concomitant to RT and TMZ in ndGBM patients. Methods: Patients with histologically confirmed ndGBM were treated with TTFields/RT/TMZ followed by maintenance TTFields and TMZ for up to 24 months. TTFields (200kHz) were delivered for >18 hours/day with removal of the transducer arrays during delivery of RT. TMZ was administered at a dose of 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined TTFields/RT/TMZ; secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Adverse events (AEs) were graded according to CTCAE V4.0. Results: Ten patients were enrolled at a single center in Israel between April and December 2017. All patients had recovered from maximal debulking surgery or biopsy. Five patients (50%) had undergone gross total resection while the rest had biopsy only. Median age was 59 and median KPS was 80. Median dose of RT was 60 Gy. Six patients (60%) reported at least one AE. The most common AE was TTFields-related skin toxicity, reported in 4 patients (40%), all of which were Grade 1-2 in severity. Two patients reported serious AEs (seizures and general deterioration) that were considered unrelated to TTFields. Median PFS with RT/TMZ/TTFields was 10.5 months. Median OS has not yet been reached. Conclusions: The proportion of patients with TTFields-related skin toxicity was similar to that reported in ndGBM patients in the randomized Phase III study (52%). No other TTFields-related toxicities were reported, nor was there an increase in RT- or TMZ-related toxicities as a result of combining TTFields with RT in addition to TMZ. Based on the safety and preliminary efficacy results of this pilot study, a Phase II randomized study has been initiated to investigate the efficacy of concomitant RT/TMZ/TTFields in 60 ndGBM patients. Citation Format: Rachel Grossman, Dror Limon, Felix Bokstein, Zvi Ram. Tumor Treating Fields combined with radiotherapy and temzolomide for newly diagnosed glioblastoma: Final results from a pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT008.

Genomic research of high grade glioma (HGG) has revealed complex biology with potential for therapeutic impact. However, the utilization of this information and impact upon patient outcome has yet to be assessed. We performed capture-based next generation sequencing (NGS) genomic analysis assay of 236/315 cancer-associated genes, with average depth of over 1000 fold, to guide treatment in HGG patients. We reviewed clinical utility and response rates in correlation to NGS results. Forty-three patients were profiled: 34 glioblastomas, 8 anaplastic astrocytomas, and one patient with anaplastic oligodendroglioma. Twenty-five patients were profiled with the 315 gene panel. The median number of identified genomic alterations (GAs) per patient was 4.5 (range 1–23). In 41 patients (95 %) at least one therapeutically-actionable GA was detected, most commonly in EGFR [17 (40 %)]. Genotype-directed treatments were prescribed in 13 patients, representing a 30 % treatment decision impact. Treatment with targeted agents included everolimus as a single agent and in combination with erlotinib; erlotinib; afatinib; palbociclib; trametinib and BGJ398. Treatments targeted various genomic findings including EGFR alterations, mTOR activation, cell cycle targets and FGFR1 mutations. None of the patients showed response to respective biologic treatments. In this group of patients with HGG, NGS revealed a high frequency of GAs that lead to targeted treatment in 30 % of the patients. The lack of response suggests that further study of mechanisms of resistance in HGG is warranted before routine use of biologically-targeted agents based on NGS results.

Use of the title “Doctor” preserves hierarchy in a patient-doctor relationship.1 However, hierarchy does not necessarily mean lack of respect, and deferential status exists in the patient-doctor relationship, regardless of whether this term is used. A similar hierarchy and relationship exist when we consult a priest, imam, rabbi, or any …

e14078Background: Tumor Treating Fields (TTFields) are a non-invasive, loco- regional, anti-mitotic treatment based on low intensity alternating electric fields. Efficacy of TTFields in newly diagn...

The optimal treatment for locally advanced laryngeal cancer remains controversial. The purpose of this trial was to determine if the response to induction chemotherapy could select patients for organ preservation protocols, and improve larynx-preservation rates without compromising overall survival (OS).The cohort comprised 12 patients with T3 disease and 14 with T4. Induction chemotherapy consisted of docetaxel, cisplatin, and 5-fluorouracil (TPF). Response to the first cycle was determined by examination and positron emission tomography (PET)-CT. Responders (50% tumor reduction) underwent chemoradiation, whereas nonresponders underwent laryngectomy.Eighty-three percent of the patients had a response and 17% had stable or progressive disease. At 2 years, the median OS was 80%, the larynx-preservation rate was 83%, and the disease-specific survival rate was 86%. Response to a single TPF cycle was associated with 2-year OS (92% vs 50%; p = .02). The T classification was not predictive of survival.Response to a single TPF-based cycle may identify patients with advanced laryngeal cancer who are amenable to organ preservation treatment. © 2016 Wiley Periodicals, Inc. Head Neck 39: 227-233, 2017.

Despite advances in radiotherapy and chemotherapy treatments for head and neck cancers, the local failure rate is high. In most radiotherapy-resistant cases, surgery is performed; however, some cases are considered unresectable. No standard treatment for these situations has been established. In this study, we review our experience with brachytherapy (BT), which has a different biological mechanism than standard radiotherapy.All patients received prior radiation to the recurrence area. Median high-dose radiation BT dose was 50 Gy, administered in 5 to 10 Gy fractions twice daily for 5 days. High-dose radiation was given via four to 10 catheters inserted under local anesthesia (3 patients) or general anesthesia with preventive tracheostomy (10 patients).Thirteen patients received BT from 2010 to 2014. Male:female ratio was 1.6:1, and median age was 66 years (range 23-89). Of those 13 patients, 10 patients were diagnosed with squamous cell carcinoma (SCC) of the oral cavity, two patients with SCC of the nasal mucosa, and one patient with eccrine duct carcinoma. Prior radiation dose ranged from 60 to 70 Gy. Local control was achieved in 11 of 13 patients; only 15.3% (2 of 13) had in-field recurrence. Five patients developed local out-of-field recurrence, and two developed distant metastases. Five patients are alive with no evidence of disease. No major toxicities were encountered. Two patients had severe mucositis and recovered within several weeks.Brachytherapy for radiotherapy-resistant head and neck cancers is feasible with minor adverse events, which enables good local control. However, many advanced head and neck cancers develop regional or distant metastases; therefore, additional treatment should be suggested.4. Laryngoscope, 126:2246-2251, 2016.

QUESTION ASKED: What is the preferred greeting process (name calling, hand shaking) in oncology practice, by patients, caregivers and medical staff? SUMMARY ANSWER: Findings suggest that patients with cancer in Israel prefer a casual environment that includes calling them by their given name and shaking hands. Yet, they prefer that physicians introduce themselves in a more formal manner, with full name and title. METHODS: A total of 186 patients and 104 caregivers visiting the outpatient clinics at the Davidoff Cancer Institute completed a questionnaire about greeting-related preferences. Similar questionnaires were completed by 93 staff members (physicians, nurses, secretaries, and psychosocial team). BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: First, our attempt to delineate the greeting process is artificial, because a human encounter is much more than just gestures. Also, this was a single-center study, and some of the subgroups were too small to analyze. Last, the answers provided by respondents were not verified by real observations of medical staff–patient meetings. REAL-LIFE IMPLICATIONS: This survey provides insights that may help oncology professionals in building relationships with their patients. Our findings of patients' preferences and ideas about the desired interactions between them and the medical staff may provide guidance on how to approach patients with cancer. Encounters between patients and medical staff are the foundation for building the patient–medical staff relationship, which is a keystone of cancer care. This survey may facilitate the initiation of such future interactions. [Table: see text]

Crizotinib achieves excellent systemic control in anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC); however, central nervous system (CNS) metastases frequently occur as an early event. Whole brain irradiation, the standard treatment, results in neurocognitive impairment. We present a case series of three ALK+ NSCLC patients with progressing CNS metastases who were treated with pulse-dose crizotinib followed by ceritinib. Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. Clinico-pathological characteristics, treatments, and outcomes were analyzed. In two patients the progression was limited to the CNS, and radiological evidence of leptomeningeal spread was present in one patient. Sequential use of crizotinib 500mg administered once daily (pulse-dose) followed by ceritinib on progression achieved control of the disease in the CNS for over 18 months and over 7 months in Patient 1 and Patient 2, respectively. This strategy provided durable CNS control after whole-brain radiotherapy failure in Patient 1, and allowed the whole-brain radiotherapy to be deferred in Patient 2. Limited CNS progression was documented in Patient 3 while he was on standard-dose/pulse-dose crizotinib for 15months; durable (over 7 months) complete remission was achieved with stereotactic radiotherapy and ceritinib. Manipulating the crizotinib schedule in ALK+ NSCLC patients with CNS metastases and using a novel ALK-inhibitor at the time of further progression may provide durable CNS control and allow brain radiotherapy to be deferred.

We evaluated the use of molecular profiling (MP) for metastatic salivary gland adenoid cystic carcinoma (SACC), for which there is no standard treatment. MP (Caris Molecular Intelligence) was performed on biopsy samples from all metastatic SACC patients attending a tertiary medical center between 2010 and 2013n=14. Treatment was selected according to the biomarkers identified. Findings were compared with all similarly diagnosed patients treated in the same center between 1996 and 2009n=9. For each patient, MP identified 1–13 biomarkers associated with clinical benefit for specific therapies (most commonly low/negative TS, low ERCC1). Eleven patients (79%) received MP-guided treatment (2 died prior to treatment initiation, 1 opted not to be treated), with complete response in 1, partial response (PR) in 3, and stable disease in 4. In the historical controls, 2 patients (22%) were treated (1 had PR). Median (range) progression-free survival in the first line after MP was 8.2 months (1.4–49.5+). Median (range) overall survival from diagnosis of metastatic disease was 31.3 (1.4–71.1+) versus 14.0 (1.5–116) months in the historical controls. In conclusion, MP expands treatment options and may improve clinical outcomes for metastatic SACC. In orphan diseases where randomized trials cannot be performed, MP could become a standard clinical tool.

Meningioangiomatosis is an uncommon nonmalignant disorder characterized by a progressive focal lesion, typically presenting as seizure disorder.1 Histologically, the lesion exhibits prominent cortical vasculature with associated perivascular mesenchymal cell proliferation. The standard treatment is surgical resection.1,2

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 1st-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.

Anaplastic thyroid carcinoma is an undifferentiated aggressive tumor with a high rate of regional and distant spread and a grave prognosis (median survival, 3 months) with no standardized treatment.To review the effect of an active treatment policy on the outcome of anaplastic thyroid carcinoma.Retrospective comparative study of all patients diagnosed as having anaplastic thyroid carcinoma and undergoing treatment from January 1, 2008, through December 31, 2013, in a tertiary university-affiliated medical center. Data were collected by medical record review. Final follow-up was completed on November 30, 2014. Data were analyzed from December 1 to 3, 2014.Treatment options included surgery and adjuvant concomitant radiotherapy and chemotherapy with doxorubicin hydrochloride or paclitaxel for local disease; full-dose chemoradiotherapy (70 Gy to the gross tumor) for local disease when surgery was not feasible; aggressive palliative radiotherapy (50 Gy to the gross tumor) for metastatic disease; and palliative radiotherapy (≤ 30 Gy) for metastatic disease with a low performance status.Survival time and quality of life.Of the 26 patients (including 15 women) who met the inclusion criteria, 11 underwent radiotherapy with curative intent. These patients included 5 who underwent curative surgery (5 with chemotherapy) and 6 who received primary chemotherapy. Nine patients received aggressive palliative radiotherapy, and 3 received palliative radiotherapy. The remaining 3 patients were not treated. Curative radiotherapy was associated with a significantly longer overall median (95% CI) survival time (11 [8.1-13.9] months) than aggressive palliative radiotherapy (6 [3.1-8.9] months), palliative radiotherapy (3 [0.0-7.8] months), and no treatment (1 month) (P .001). Chemotherapy in 10 patients had a significant effect on survival (mean [95% CI], 11 [1.2-6.8] vs 4 [8.1-13.9] months for patients who did not receive chemotherapy; P = .01). Among the patients who underwent surgery and curative radiotherapy, 3 were alive after more than 3 years of follow-up. No association of survival with patient sex (median [95% CI] survival for men and women, 9 [3.6-14.4] and 5 [0.3-9.7] months, respectively; P = .54) or a history of thyroid disease (median [95% CI] survival for those with and without, 4 [1.0-6.9] and 9 [5.4-12.5] months, respectively; P = .15) was found.Anaplastic thyroid carcinoma has a grave prognosis, but an aggressive approach, including surgery, chemotherapy, and radiotherapy, seems to improve survival. Higher doses of radiotherapy may have a survival benefit in candidates for palliative treatment and may be considered for patients with extensive disease.