Search

For the past two decades an increasing number of oropharyngeal cancers have been found to be associated with the human papilloma virus (HPV). These tumors are a biologically distinct entity with better prognosis and excellent response to therapy. Therefore, a separate staging system has been introduced for HPV-related oropharyngeal tumors in the latest edition of the American Joint Committee on Cancer (AJCC eighth Ed).

Importance This study reports the impact of laser surgery on quality of life in patients with oral cavity lesions. Objective To compare postoperative pain and quality of life in patients treated with flexible fiberoptic CO2 laser vs electrocautery in patients with oral cavity precancerous lesions and early stage cancers. Design Randomized controlled trial. Setting Single center. Participants Patients with premalignant oral cavity lesions and early stage oral cancer. Intervention Patients were randomized to have surgical resection using either flexible fiber carbon dioxide laser (Laser) or electrocautery (EC). The patients were then followed over a period of 28 days to assess for outcomes including pain, quality of life, performance status, return to work, and return to diet. Quality of life was measured by the University of Washington Quality of Life (UWQOL) questionnaire and the performance status score (PSS). Main outcome measure The primary endpoint for this study was the numerical pain rating on postoperative day (POD) 7. Results Sixty‐two patients were randomized (32 laser and 30 electrocautery). Lesions excised were carcinoma in 30(48%), dysplasia in 31(50%) and benign in 1(2%). There was no difference in the location of lesion, size of lesion, defect size, type of closure, resection time, and blood loss between Laser and EC arms. Patients who had Laser had less pain compared to EC (mean pain score on POD 7 L = 2.84 vs EC = 3.83, P = 0.11). better UW QOL scores and PSS scores, quicker return to normal diet (median days L = 26.0 vs EC = 28.5, P = 0.17) and faster return to work (median days L = 13.0 vs EC = 16.5, P = 0.14). However, these results were not statistically significant. Conclusion There was a trend for patients treated with laser to have less pain and better quality of life scores but these result were not statistically significant. Based on the actual observed difference, a large multicenter RCT with 90 patients in each arm is required to determine the clinical relevance of our results.

BACKGROUND: Considering the pandemic's mode of transmission, the impact on quality of life (QOL) is likely to be exaggerated among healthcare workers (HCWs) who treat head and neck diseases (hHCWs). METHODS: A cross-sectional self-reported QOL assessment was undertaken between July and September 2020 using the World Health Organization Quality of Life instrument sent out to hHCWs. Factors that predicted a poorer QOL were identified using regression models and mediation analysis. RESULTS: Responses from 979 individuals across 53 countries were analyzed with 62.4% participation from low- and middle-income countries. The physical domain had the highest mean scores of 15 ± 2.51, while the environmental domain was the lowest (14.17 ± 2.42). Participants from low- and middle-income countries had a significantly worse physical (p < 0.001) and environmental (p < 0.001) domains, while a low coronavirus disease 2019-related mortality significantly impacted the environmental domain (p-0.034). CONCLUSION: QOL-related issues among hHCWs are a vexing problem and need intervention at an individual and systems level in all parts of the world.

SummaryBackground Selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound inhibits Exportin-1(XPO1), had demonstrated synergistic activity with many chemotherapies and conferred in vivo antitumor efficacy in hematologic as well as solid tumors. Methods This open-label, single-center, multi-arm phase 1b study used a standard 3 + 3 design and a “basket type” expansion. Selinexor with intravenous topotecan was given in one of the 13 parallel arms. Patients with advanced or metastatic relapsed/refractory solid tumors following prior systemic therapy, or in whom the addition of selinexor to standard chemotherapy deemed appropriate, were eligible. Results Fourteen patients with the median age of 61 years (range, 22–68years) were treated, and the most common cancer types were gynecological cancers; ovarian (n = 5), endometrial (n = 2), and 1 each with fallopian tube and vaginal cancers. Of the 14 patients treated, 12 (86 %) had at least one treatment-related adverse event (TRAE). The most common TRAEs were anemia (71 %), thrombocytopenia (57 %), hyponatremia (57 %), vomiting (57 %), fatigue (50 %), nausea (50 %), and neutropenia (36 %). Two patients had dose limiting toxicities. One patient dosed at selinexor 80 mg had grade 3 nausea and vomiting and one patient dosed at selinexor 60 mg experienced grade 4 neutropenia and thrombocytopenia. Of the 13 efficacy evaluable patients, one (8 %) with endometrial cancer achieved unconfirmed partial response (uPR) and the time-to-treatment failure (TTF) was 48 weeks, whereas 6 of the 13 (46 %) patients had stable disease (SD) contributing to the clinical benefit rate of 46 %. The median TTF for all patients was 9 weeks (range, 2–48weeks). Conclusions Once weekly selinexor in combination with topotecan was viable and showed some preliminary tumor efficacy. The recommend phase 2 dose of selinexor was 60 mg once weekly in combination with IV topotecan.Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Purpose: The nuclear exporter protein exportin-1 (XPO1) is overexpressed in non-Hodgkin lymphoma (NHL) and correlates with poor prognosis. We evaluated enhancing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) activity in NHL by targeted inhibition of XPO1 using the selective inhibitor of nuclear export (SINE) compounds. Patients and Methods: We evaluated the antitumor activity of SINE compounds in combination with CHO chemotherapy in vitro and in vivo. Newly diagnosed NHL patients in a phase I dose-escalation study received R-CHOP for 6 cycles with weekly selinexor (60, 80, and 100 mg), then selinexor maintenance therapy for one year. RT-PCR, Western blotting, and RNA sequencing were performed on patient blood samples. Results: SINE compounds synergized with CHO in vitro in NHL cell lines and in vivo in our murine xenograft model. In our phase I study, selinexor was dosed at 60 mg (n = 6) and 80 mg (n = 6). The most common adverse events (AE) among 12 patients were fatigue (67%) and nausea (100%). Grade 3–4 AEs were infrequent. Ten evaluable patients had an overall response rate of 100% and complete remission rate of 90% with sustained remissions (median follow-up: 476 days). Maximally tolerated dose was not reached; however, the recommended phase II dose was 60 mg selinexor weekly after evaluating tolerability and discontinuation rates for each dose cohort. Analysis of patient blood samples revealed downregulation of XPO1 and several prosurvival markers. Conclusions: SINE compounds enhance the activity of CHO in vitro and in vivo. Selinexor in combination with R-CHOP was generally well tolerated and showed encouraging efficacy in NHL (NCT03147885).

Objective This study was aimed to describe our institutional experience on characteristics and treatment outcomes of sinonasal sarcomas invading the anterior skull base. Design Present study is a retrospective review. Setting The study was conducted at an academic cancer care center. Participants Thirty-one patients with skull base sarcomas treated with primary surgery from 1979 to 2015 were identified for this study from a preexisting database. Main Outcome Measures Survival and recurrence outcomes using the Kaplan–Meier method were the focus areas of the study. Results The median age was 44 years (range: 13–69 years). Twenty patients were male (64.5%). Twenty-nine patients underwent open craniofacial resection (93.5%) and two patients underwent endoscopic resection (6.5%). The majority of tumors were staged pT4 (77.4%). The most common pathologies were leiomyosarcoma (19.4%), osteosarcoma (16.1%), and chondrosarcoma (12.9%). Of those with known margin status, 10 patients had positive/close margins (32.2%) and 16 patients had negative margins (51.6%). Most tumors were high grade (74.2%). Twenty-three patients (74.2%) received adjuvant radiation and four patients (12.9%) received adjuvant chemotherapy. There were nine postoperative complications (29%) including one mortality and three cerebrospinal fluid leaks. There were 10 local, 2 regional, and 5 distant recurrences over a median follow-up of 74 months (range: 1–300 months). The 5-year disease-specific survival (DSS) was 69.8%. The 5-year locoregional recurrence-free probability (RFP) was 63.2% and the 10-year distant RFP was 71.7%. The 5-year DSS for high grade tumors was 64.2 and 85.7% for low grade tumors (p = 0.117). Conclusion This study contributes an updated analysis of anterior skull base sarcomas. Five-year DSS is approximately 70%. Analysis of survival outcomes based on grade, tumor size, and other factors is limited by small sample size and the rarity of these tumors.

OBJECTIVE. To address the lack of validated patient-reported outcome (PRO) instruments that define and quantify patient expectations in thyroid cancer surgery, we developed and initially validated ThyroidEx, a novel disease-specific PRO instrument. STUDY DESIGN. Survey study. SETTING. Single-institution tertiary care cancer center. METHODS. An expert panel drafted an initial set of thyroid cancer–specific concepts, which was used in semistructured concept elicitation interviews with patients with thyroid cancer 4 weeks before and 8 weeks after surgery. Candidate items were generated per patient responses and refined via cognitive interviewing and additional review by the expert panel. The draft ThyroidEx was then preoperatively administered to a separate cohort undergoing thyroid cancer surgery to establish a final item set and initial psychometric evidence. RESULTS. Prospective concept elicitation interviews generated 358 patient-elicited concepts (n = 15 patients). These were then placed into 70 unique subcategories from which 41 items were generated for cognitive interviews with 20 patients preoperatively and 28 postoperatively. After expert panel review, ThyroidEx included 18 items across 2 scales (Expectations and Concerns), with an additional item about beliefs. In the preoperative cohort in phase 2 (n = 67), internal consistency Cronbach’s α values ranged from 0.81 to 0.89. Descriptive analysis showed significant differences between patients’ concerns and expectations and clinicians’ perceptions. CONCLUSION. Defining expectations represents an important modifier in the measurement of PROs. Preliminary validation of ThyroidEx revealed incongruent expectations between expert opinion and patients. Future development and implementation of ThyroidEx may affect preoperative consultation and the consent process.

We assessed the safety, efficacy, maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of selinexor, a first in class oral selective inhibitor of nuclear export (100 mg once weekly [QW] or 60 mg twice weekly), in combination with daratumumab (16 mg/kg per label) and dexamethasone (40 mg QW) (SDd) in patients with relapsed refractory multiple myeloma (RRMM). Thirty-four patients (median prior therapies, 3 [range, 2-10]) were enrolled; MM was refractory to proteasome inhibitor (PI) in 85%, immunomodulatory agent (IMiD) in 76%, both in 74%, and daratumumab in 6% of patients. Two dose-limiting toxicities (DLTs) were reported in the selinexor 60 mg twice-weekly cohort with no DLTs in the 100 mg QW cohort, making 100 mg QW the MTD and RP2D. Common treatment-related adverse events included thrombocytopenia (70.6%), nausea (70.6%), fatigue (61.8%), anemia (61.8%), and neutropenia (50.0%). Overall response rate was 73% and median progression-free survival 12.5 months in daratumumab-naïve patients. SDd was well tolerated and its promising efficacy suggests that further study of this PI- and IMiD-free regimen in RRMM patients who had at least one prior line of therapy including a PI and an IMiD but whose disease is naïve to daratumumab is warranted.

BACKGROUND: Sinonasal malignancies are a complex and diverse group of tumors. Over the past five decades, treatment advances have changed the management paradigms for these tumors. Our aim was to analyze the outcomes of patients from a comprehensive cancer center. MATERIALS AND METHODS: We retrospectively assessed 400 patients with sinonasal malignancies treated with surgery at our center between 1973 and 2015. Multiple variables were reviewed to assess the influence on 5-year outcomes. RESULTS: The median age was 56 years (IQR 46.8–68). Two hundred and fifty-nine (65%) were males and 141 (35%) were females. Overall survival (OS) and disease-specific survival (DSS) improved in the last analyzed decade. Orbital invasion, advanced pT-classification and pN-classification, and melanoma histology were associated with poorer outcomes. CONCLUSION: Treatment outcomes for patients with sinonasal malignancy have improved over time. This is likely multifactorial with advances in surgical technique, adjuvant treatment, and patient selection. pT-classification, pN-classification, orbital invasion, and histology are predictive of survival.

Endoscopic endonasal surgery has been demonstrated to be effective in the treatment of selected cases of sinonasal cancers. However, in cases of locally advanced neoplasms, as well as recurrences, the most appropriate approach is still debated. The present review aims to summarize the current state of knowledge on the utility of open approaches to resect sinonasal malignant tumours. Published comparative studies and meta-analyses suggest comparable oncological results with lower morbidity for the endoscopic approaches, but selection biases cannot be excluded. After a critical analysis of the available literature, it can be concluded that endoscopic surgery for selected lesions allows for oncologically safe resections with decreased morbidity. However, when endoscopic endonasal surgery is contraindicated and definitive chemoradiotherapy is not appropriate, craniofacial and transfacial approaches remain the best therapeutic option.

The phase 2b, open-label, multicenter SADAL study evaluated single agent oral selinexor, a selective inhibitor of nuclear export (SINE) compound, in patients with diffuse large B cell lymphoma (DLBCL) after >= 2 lines of systemic therapy. Similar activity was observed in GCB- and non-GCB DLBCL with a trend to higher response rates in DLBCL transformed from follicular lymphoma. Lower response rates were observed in double expressor DLBCL; higher response rates were observed in patients with baseline hemoglobin >= 10 g/dL and normal levels of C-MYC or BCL-2 expression (51%). Overall, strong single agent activity with selinexor were observed in patients with relapsed/refractory DLBCL.Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels >= 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin. (C) 2021 Elsevier Inc. All rights reserved.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with high mortality. Identifying patients at risk of distant metastasis assists with management and prognostication. We aimed to define the relationship between volume, survival, and risk of distant metastases. METHODS: A retrospective review of all patients with SNMM treated at a single institution over a 21-year period was conducted. Tumor volume was calculated using cross-sectional imaging and survival analysis was performed. RESULTS: Sixty-one patients were included. Tumor volume was predictive of local progression free survival (LPFS) (p=0.032), distant metastases free survival (DMFS) (p=0.002), and overall survival (OS) (p=0.022). It was a better predictor than AJCC stage and T-classification. Tumor volume equal to or greater than 5cm(3) was associated with a significantly worse DMFS and OS (p=0.022 and 0.009, respectively). CONCLUSION: Calculation of tumor volume assists in quantifying the risk of distant metastases and death in SNMM.

BACKGROUND: The 2015 American Thyroid Association guidelines state that a prophylactic central compartment neck dissection (PCND) should be considered for patients with papillary thyroid carcinoma (PTC) and clinically involved lateral neck lymph nodes (cN1b). The aim of our study was to determine the rate of central neck recurrence in select cN1b patients, with no evidence of clinically involved central compartment lymph nodes, treated without a PCND. METHODS: After institutional review board approval, adult PTC patients with cN1b disease who were treated with a total thyroidectomy and lateral neck dissection were identified from an institutional database of 6,259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, and no pre-operative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on pre-operative imaging or intra-operative evaluation, were also excluded. One hundred fifty-two cN1b patients were included and categorized into non-PCND and PCND groups. Central neck recurrence-free probability (CNRFP) was calculated using the Kaplan-Meier method and log-rank tests. RESULTS: One hundred three patients (67.8%) did not have a PCND. With a median follow-up of 65 months, the 5- and 10-year CNRFP was 98.4% in the non-PCND group and 93.6% in the PCND group (p = 0.133). CONCLUSIONS: Select PTC patients with cN1b disease but no evidence of clinically involved central compartment lymph nodes, on pre-operative imaging and intra-operative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID‐19) pandemic, government‐mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in‐person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard‐of‐care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high‐volume cancer center at the domestic epicenter of the COVID‐19 crisis., Cancer care is undeniably affected by the coronavirus disease 2019 (COVID‐19) public health emergency, but quality cancer care must persist. A high‐volume cancer center from the domestic epicenter of the COVID‐19 crisis shares its multidisciplinary approach to integrating current public health restrictions and adopting telemedicine to optimize the care of patients with head and neck cancer; it is hoped that this center's experience will provide helpful insights to oncology colleagues.

BACKGROUND: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. METHODS: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). FINDINGS: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7-37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. INTERPRETATION: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. FUNDING: Karyopharm Therapeutics Inc.

INTRODUCTION: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. METHODS: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients. RESULTS: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor at presentation and the opinion of experienced clinicians. CONCLUSION: These aggressive variants should be known by clinicians, to avoid underdiagnosis, and treated according to the latest recommendations in the literature. ispartof: ADVANCES IN THERAPY vol:37 issue:7 pages:3112-3128 ispartof: location:United States status: published

Background We aimed to review our experience and the changing trends in the management of head and neck paragangliomas (HNPG) over the last three decades. Methods We retrospectively reviewed 103 patients with HNPG treated at our center (1986-2017). We included patients treated with surgery, radiotherapy, and patients maintained under active surveillance. Results Of the surgically treated patients (n = 79), 20% (12/59) of the carotid body tumors (CBT) had a cranial nerve deficit as sequela compared to 95% (19/20) of the non-CBT. Radiotherapy controlled growth in all tumors treated with this modality (n = 10). Of the initially observed patients, 70% (14/20) remained stable and did not require additional treatment. Stratifying by decades, there was a progressive increase in patients initially attempted to be observed and a decrease in upfront surgery. No deaths attributable to the HNPG were encountered. Conclusions Surgery is an effective treatment for CBT. Nonsurgical treatment should be considered for non-CBT.

Background: Retropharyngeal lymph node metastases (RPMs) from differentiated thyroid carcinoma (DTC) are rare. Treatment includes surgical resection, radioactive iodine (RAI) therapy, or external beam radiation therapy (EBRT). The objective of this study was to describe our experience in the management of DTC-associated RPMs. Methods: Patients diagnosed with a DTC-associated RPM from 1999 to 2018 were identified at our institution, using key search terms in imaging and histology reports. Patient and tumor characteristics were recorded, and patients were grouped according to RPM management: observation, nonsurgical treatment, or surgical resection. The estimated rates of local RPM control, disease-specific survival (DSS), and distant metastasis-free probability (DMFP) were calculated by using the Kaplan-Meier method. Results: Of the 65 patients identified, 53 (82%) had an RPM as a manifestation of recurrent disease. Twenty-five patients (38%) underwent observation, 13 (20%) received nonsurgical treatment (RAI, EBRT, and/or systemic therapy), and 27 (42%) underwent surgical resection. In the observation cohort, all patients had a stable RPM, which in the majority (80%) of cases remained

Background and Objectives The number of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) at an advanced age has increased. The aim of this study is to evaluate the age at which disease-specific survival (DSS) significantly decreases in HNSCC. Methods We performed a retrospective study of 5469 patients with HNSCC treated at our center (1985-2016). External validation with 2082 oral squamous cell carcinomas from a collaborative institution from another continent was performed. Results We observed an orderly decrease in overall survival as age at diagnosis increased. There were no differences in DSS based on age for patients 85 had a 2.19 times higher risk (95% CI: 1.68-2.87; P < .001). Conclusions DSS started to significantly decrease in HNSCC at 80 years old. These findings, validated in an independent cohort, indicate that chronological age on its own should not withhold curative treatment in the majority of patients with HNSCC.

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1–2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.

Background Multifocality in papillary thyroid carcinoma is common. The aim of this study is to determine whether patients with multifocal disease, treated with lobectomy alone, have an increased risk of contralateral lobe papillary thyroid carcinoma, regional recurrence, and poorer survival. Methods After institutional review board approval, papillary thyroid carcinoma patients managed from 1986 to 2015 with lobectomy alone were identified from an institutional database. Papillary thyroid carcinoma patients with pT3 to T4 classification, nodal disease, or distant metastases were excluded. After excluding 40 patients who underwent an immediate completion thyroidectomy, 849 were included in the analysis; 619 (72.9%) had unifocal disease and 230 (27.1%) had multifocal disease. Contralateral lobe papillary thyroid carcinoma-free probability, regional recurrence-free probability, disease-specific survival, and overall survival were calculated using the Kaplan-Meier method. Results With a median follow-up of 58 months, unifocal disease and multifocal disease patients had similar rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival (10-year contralateral lobe papillary thyroid carcinoma-free probability 98.6% vs 97.8%; regional recurrence-free probability 99.5% vs 99.4%; overall survival 91.6% vs 93.1%, respectively). There were no disease-related deaths. Conclusion Select multifocal disease patients, managed with lobectomy alone, have rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival comparable to unifocal disease patients. Multifocal disease should not be an indication for completion thyroidectomy.

Background This study aims to evaluate the impact of perioperative fluid administration, defined as fluid delivered intraoperatively and in the postanesthesia care unit, on postoperative outcomes. Methods Medical records of 102 patients with oral cavity squamous cell carcinoma undergoing free flap reconstruction between January 2011 and December 2015 were reviewed. The primary endpoint was development of a postoperative complication according to the Clavien-Dindo classification. Perioperative factors recorded were Washington University Head and Neck Comorbidity Index, operating time, vasopressor use, blood loss, intraoperative fluid, and perioperative fluid. Results Greater perioperative fluid administration was independently associated with surgical complications, flap complications, overall incidence of any complication, and increased length of stay. Greater intraoperative fluid administration was independently associated with higher rates of surgical complications. Intraoperative delivery of vasopressors was not associated with flap or surgical complications. Conclusion Receiving less perioperative fluid was associated with fewer complications and decreased length of stay.

Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies. Our aim was to evaluate the prognostic impact of primary tumor site in patients with MEC. Material and Methods This cohort identified 308 patients with MEC who underwent primary surgery between 1985 and 2015. Survival outcomes were determined using the Kaplan–Meier method. Hazard ratios for primary site were determined using the Cox proportional-hazards model. Results One hundred eighty (58%) patients were diagnosed with minor and 128 (42%) with major salivary gland cancer. Primary site in the minor salivary gland group included 137 (44%) oral cavity, 38 (12%) pharynx, 3 (0.9%) nasal cavity, and 2 (0.6%) trachea and larynx. The major salivary gland group included 118 (38%) parotid, 8 (3%) submandibular, and 2 (0.6%) sublingual. With a median follow-up of 73 months, 5-year overall survival and disease-specific survival were 84% and 91%, respectively. Patients with tumors located in the hard palate and retromolar trigone had the best survival, while patients with tumors located in the paranasal sinuses and submandibular gland had the poorest survival. After controlling for tumor grade and stage, MEC primary site was not predictive of survival or recurrence. On multivariate analysis, worse DSS was associated with stage III–IV tumors (HR: 7,11; 95% CI: 1.19–26.43; p = 0.0034) and high-grade tumors (HR: 19.12; 95% CI: 2.26–162.77; p = 0.0068). Conclusions While high grade and advanced overall stage were found to be independent predictors of worse survival, primary tumor site was not predictive of poor outcome.

Background Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy – Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. Methods FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. Results Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. Conclusion The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. Trial registration This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.

Selinexor, a selective inhibitor of nuclear export, has demonstrated promising activity in patients with acute myeloid leukemia (AML). This randomized, phase II study evaluated selinexor 60 mg twice weekly ( n = 118) vs. physician's choice (PC) treatment ( n = 57) in patients aged =60 years with relapsed/refractory (R/R) AML. The primary outcome was overall survival (OS). Median OS did not differ significantly for selinexor vs. PC (3.2 vs. 5.6 months; HR = 1.18 [95% CI: 0.79-1.75]; p = 0.422). Complete remission (CR) plus CR with incomplete hematologic recovery trending in favor of selinexor occurred in a minority of patients. Selinexor treated patients had an increased incidence of adverse events. The most common grade =3 adverse events were thrombocytopenia, febrile neutropenia, anemia, hyponatremia. Despite well-balanced baseline characteristics, there were numerically higher rates of TP53 mutations, prior myelodysplastic syndrome, and lower absolute neutrophil counts in the selinexor group; warranting further investigation of selinexor in more carefully stratified R/R AML patients. Registered trial: NCT02088541.

Patients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of < 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were ≥ 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months (p < 0.0001). Patients < 70 years had an OS of 11.1 months compared with 7.8 months in patients ≥ 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be < 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned. This trial was registered at ClinicalTrials.gov (NCT02227251) on August 28, 2014. https://clinicaltrials.gov/ct2/show/NCT02227251., SCOPUS: le.j, info:eu-repo/semantics/published

Background Proteasome inhibitors (PIs), including carfilzomib, potentiate the activity of selinexor, a novel, first-in-class, oral selective inhibitor of nuclear export (SINE) compound, in preclinical models of multiple myeloma (MM). Methods The safety, efficacy, maximum-tolerated dose (MTD) and recommended phase 2 dose (RP2D) of selinexor (80 or 100 mg) + carfilzomib (56 or 70 mg/m2) + dexamethasone (40 mg) (XKd) once weekly (QW) was evaluated in patients with relapsed refractory MM (RRMM) not refractory to carfilzomib. Results Thirty-two patients, median prior therapies 4 (range, 1–8), were enrolled. MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and/or gain 1q. Common treatment-related adverse events (all/Grade 3) were thrombocytopenia 72%/47% (G3 and G4), nausea 72%/6%, anaemia 53%/19% and fatigue 53%/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all QW. The overall response rate was 78% including 14 (44%) ≥ very good partial responses. Median progression-free survival was 15 months. Conclusions Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.

SummaryBackground. Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies. Methods. This was a single-center, multi-arm phase Ib study utilizing a “basket type” expansion. CT and selinexor was employed as one of the 13 parallel arms. Advanced relapsed/refractory solid tumors following standard therapy or where the addition of selinexor to standard regimens deemed appropriate, were eligible. Results. Of 13 patients treated, 12 patients were evaluable for response. The most common cancers were breast (n = 4), esophageal (n = 2), ovarian (n = 2) and non-small cell lung cancers (n = 2). All 13 patients had at least one treatment-related adverse events (TRAEs) and the most common were neutropenia (85%), leukopenia (85%), thrombocytopenia (85%), anemia (69%), nausea (54%), vomiting (46%), and fatigue (46%). One patient at 60 mg QW experienced DLT with grade 3 nausea and vomiting lasting 3 days. Unconfirmed partial response (uPR) was observed in 3 patients; one patient each with esophageal, breast, and ovarian cancer. One patient with esophageal adenocarcinoma had confirmed PR, however, was discontinued from the study due to clinical progression. Five patients achieved stable disease (SD). Disease control rate was 8%. Majority of patients (77%), including two patients who had uPR, had prior exposure to carboplatin and/or paclitaxel. Time-to-treatment failure (TTF) ranged from 1 to 153 weeks. Conclusion. The RP2D of selinexor was 60 mg QW in combination with CT. The combination conferred viable clinical activity with durable objective responses which should further be explored in tumor types for which CT is used as standard of care. Trial information. ClinicalTrials.gov Identifier: NCT02419495. Sponsor(s): Karyopharm Therapeutics. (Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495).

Introduction Selinexor is a first-in-class, oral, potent selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, leading to cancer cell apoptosis. Selinexor has demonstrated antimyeloma activity in triple class refractory multiple myeloma (MM) [Chari et al. NEJM 2019]. Selinexor synergizes with proteasome inhibitors (PIs) in PI-sensitive and -resistant cell lines and produces high response rates in patients with PI refractory and non-refractory MM (Bahlis et al. Blood 2018). In the phase 3 BOSTON study, the combination of once weekly (QW) selinexor, QW bortezomib, and dexamethasone (SVd) in patients who had received 1-3 prior therapies led to a significantly longer (47%) median progression-free survival (PFS) of 13.93 vs 9.46 months, with a hazard ratio of 0.70 (P=0.0075) compared to standard twice weekly bortezomib and dexamethasone (Vd). In addition, SVd regimen produced higher response rates and deeper responses (ORR: 76.4% vs 62.3% and ≥CR 16.9% vs 10.2%) compared with Vd. The benefit with SVd was observed across all efficacy endpoints and was associated with lower incidence and severity of bortezomib-induced peripheral neuropathy. Here we analyzed the effect of prior PI therapy (bortezomib, carfilzomib, ixazomib) on the efficacy and safety of SVd compared with Vd. Methods BOSTON is an open-label, randomized phase 3 study in patients with MM comparing SVd (QW oral selinexor 100 mg, QW subcutaneous bortezomib 1.3 mg/m2, and BIW oral dexamethasone 20 mg), versus Vd (BIW bortezomib 1.3 mg/m2 and QIW dexamethasone 20 mg). Patients previously treated with a PI must have had at least a partial response (PR) to the PI and 6 months since the last PI regimen. The study primary end point was PFS. Here we report subgroup analysis of treatment outcomes based on prior PI treatment. Results Subgroups consisted of PI naïve patients (n=95; 24%) and patients with prior PI treatment (n=307; 76%). Both the subgroups and study arms were comparable for baseline patient demographic and disease characteristics. However, those with prior PI treatment more frequently had a previous stem cell transplant (38% vs 24%) or 3 lines of prior anti MM therapy (21% vs 13%). Median PFS was improved with SVd compared with Vd in both the PI naïve group (PFS not reached (NR) vs 9.7 months; HR 0.2585 [95% CI, 0.1116-0.5988]; P=0.0003) and in the PI treated group (11.7 vs 9.4 months; HR 0.7839 [95% CI, 0.5791-1.0612]; P=0.06). Other efficacy endpoints are shown in the table. Peripheral neuropathy ≥grade 2 (a secondary study endpoint) was less frequent in the SVd compared with the Vd arm (PI naïve: 25.5%, Vd 43.8%, P=0.0302; PI treated: SVd 19.6%, Vd 31.4%, P=0.0092). Adverse events of ≥grade 3 occurred in 71% of patients in the PI naïve group (SVd 77%, Vd 65%) and 74% of patients in the PI treated group (SVd 88%, Vd 60%). Thrombocytopenia was more frequent in patients in the SVd arms (PI naïve: SVd 32%, Vd 13%; PI treated: SVd 42%, Vd 19%) as was anemia (PI naïve: SVd 15%, Vd 6%; PI treated: SVd 16%, Vd 12%), and fatigue (PI naïve: SVd 15%, Vd 2%; PI treated: SVd 13%, Vd 1%). Conclusions The once-weekly SVd combination was associated with significant clinical benefit and reduced peripheral neuropathy as compared with standard twice-weekly Vd in patients with MM and 1-3 prior therapies, regardless of prior therapy with a PI. However, the benefits of SVd over Vd were more pronounced in patients who had never been treated with a PI (PFS HR 0.26), suggesting that selinexor could be an optimal partner for combining with weekly bortezomib as the first PI-containing MM regimen. Figure 1 Disclosures Mateos: Roche: Honoraria; Seattle Genetics: Honoraria; EDO Mundipharma: Honoraria; Adaptive Biotechnologies: Honoraria; GlaxoSmithKline: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Auner:Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Leleu:AbbVie: Honoraria; GSK: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria; Oncopeptide: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria. Hajek:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, Janssen: Consultancy; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses; Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Moreau:Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Honoraria. Levy:Karyopharm,Takeda, BMS: Consultancy, Honoraria, Speakers Bureau. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:Karyopharm: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis:Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; AbbVie: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

Introduction Selinexor is a first-in-class, oral, potent selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, leading to cancer cell apoptosis. Selinexor has demonstrated antimyeloma activity in triple class refractory multiple myeloma (MM) [Chari et al. NEJM 2019]. Selinexor synergizes with proteasome inhibitors (PIs) in PI-sensitive and -resistant cell lines and produces high response rates in patients with PI refractory and non-refractory MM. (Bahlis et al. Blood 2018). In the phase 3 BOSTON study, the combination of once weekly (QW) selinexor, QW bortezomib and dexamethasone (SVd) in patients who had received 1-3 prior therapies led to a significantly (47%) longer median progression-free survival (PFS) of 13.93 versus 9.46 months (HR 0.70; P=0.0075) compared to standard twice weekly bortezomib and dexamethasone (Vd). In addition, SVd regimen produced higher response rates and deeper responses (ORR: 76.4% vs 62.3% and ≥CR 16.9% vs 10.2%) compared with Vd. The benefit with SVd was observed across all efficacy endpoints and was associated with lower incidence and severity of bortezomib-induced peripheral neuropathy. Here we present subgroup analyses according to number of prior lines of therapy and prior treatment with lenalidomide (LEN). Methods BOSTON is an open-label, randomized phase 3 study in patients with MM comparing SVd (QW selinexor 100 mg, QW subcutaneous bortezomib 1.3 mg/m2, and 20 mg twice weekly [BIW] dexamethasone), versus Vd (1.3 mg/m2 bortezomib BIW and dexamethasone 20 mg 4 x weekly [QIW]). Patients previously treated with a PI must have had at least a partial response (PR) to the PI and 6 months since the last PI regimen. The study primary end point was PFS. Results Of the 402 patients in the BOSTON study, 198 (49%) had 1 prior line versus 204 (51%) with 2-3 prior lines. In addition, 154 (38%) comprised the LEN treated subgroup, versus 248 (62%) in the LEN naïve subgroup. Of note, 41% patients received prior thalidomide, which is consistent with most of the BOSTON study patients being treated in the EU. Baseline demographic and disease characteristics were well balanced between treatment arms across subgroups. A very good partial response (VGPR) or better to most recent prior line anti-MM therapy was more frequent in patients with 1 prior line of therapy (63% vs 41%) versus those with 2-3 prior lines of therapy. Patients with prior LEN therapy were more likely to have had 2-3 prior therapies (72.1%) compared with LEN naive patients (37.5%). As shown in the table, SVd was associated with longer PFS compared with Vd in all subgroups. Overall response rates (ORR) and times-to-next-treatment (TTNT) were statistically greater with SVd compared with Vd in all subgroups. Rates of very good partial response or better (VGPR) were statistically greater for SVd vs Vd in the LEN-naïve group and 1 prior treatment group. Grade ≥2 peripheral neuropathy (a key secondary endpoint prespecified in the study) occurred less frequently across all SVd subgroups compared with Vd: LEN treated (21% SVd, 37% Vd, P=0.0166); LEN-naïve (21% SVd, 33% Vd, P=0.0252), 1 prior line (21% SVd, 33% Vd, P=0.0501); 2-3 prior lines (21% SVd, 36% Vd, P=0.0107). Adverse events of ≥grade 3 were more commonly reported in the SVd treatment arm than in the Vd arm, LEN treated (83% SVd, 57% Vd), LEN-naïve (76% SVd, 55% Vd), 1 prior line (77% SVd, 56% Vd), 2-3 prior lines (81% SVd, 56% Vd), and were mostly managed with dose modification and/or supportive treatment. Pneumonia occurred at comparable rates between treatment arms. There were no differences between subgroups in grade 3 adverse events. Conclusions In the BOSTON study, once-weekly SVd significantly improved PFS, ORR, TTNT and reduced rates of ≥grade 2 peripheral neuropathy compared with Vd regardless of number of prior treatments or whether patients were previously treated with LEN. Adverse events were managed with dose modification and treatment-related discontinuation rates did not differ between the 2 regimens for any subgroup. The PFS of 16.6 months with SVd after 1 prior therapy, and the HR of 0.63 in patients with prior LEN treatment support the use of once-weekly SVd for the second line treatment of MM following a LEN-containing regimen. Table Disclosures Mateos: Takeda: Honoraria; Abbvie: Honoraria; GlaxoSmithKline: Honoraria; EDO Mundipharma: Honoraria; Seattle Genetics: Honoraria; Roche: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria. Jagannath:Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding; Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses; Takeda, Janssen: Consultancy. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Dimopoulos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees. Auner:Amgen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Leleu:BMS-celgene: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; AbbVie: Honoraria; Oncopeptide: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; GSK: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding. Moreau:Novartis: Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Levy:Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment; Takeda: Consultancy, Honoraria, Research Funding. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Bahlis:Genentech: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; Sanofi: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.

Background: The approach for surgical treatment of patients with low-/intermediate-risk T1T2N0/Nx well-differentiated thyroid cancer (WDTC)—total thyroidectomy (TT) versus thyroid lobectomy (TL)—remains a controversial topic. Conducting a randomized controlled trial (RCT) would be the gold standard to address this issue. However, this is challenging due to excellent survival outcomes, and therefore, high number of patients and long-term follow-up would be required. As an alternative to RCT, we have used propensity score (PS) matching to determine if T1T2N0/Nx patients selected to have TL had equivalent outcomes to a similar group treated with TT. Methods: After institutional review board approval, a database of 6259 patients with WDTC treated with primary surgery at our institution between 1985 and 2016 was analyzed to identify patients with T1T2N0/Nx cancers. Of 3756 patients identified, 943 were managed by TL and 2813 by TT. To control for possible confounders and reduce potential bias, we selected age, sex, histology, (131)I therapy, American Thyroid Association risk, and American Joint Committee Cancer stage as our PS matching criteria. Subsequently, 918 TL patients were successfully matched with 918 TT patients. The Pearson χ(2) test or Fisher's exact test was used to compare categorical covariates, and Student's t-test was used for comparison of continuous variables between the two groups. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: After PS matching, there were no significant differences between TL and TT patients for OS (10-year OS: 92.2% vs. 91.3%, p = 0.9668), DSS (10-year DSS: 100% vs. 99.1%, p = 0.1967), or RFS (10-year RFS: 99.5% vs. 98.3%, p = 0.079). Conclusions: For low-/intermediate-risk patients with intrathyroidal thyroid cancer

Objectives Sinonasal and skull base tumors are rare, making it difficult to identify trends in surgical outcome. This study examines complications in a large cohort of patients undergoing surgery for sinonasal malignancy. Methods Following IRB approval, an institutional database was reviewed to identify patients who underwent surgery for sinonasal or skull base malignancies from 1973 to 2016 at our institution. Charlson comorbidity index score and Clavien-Dindo grade were calculated. The main study endpoint was subgroup analysis of Clavien-Dindo Grade 0, Grades 1-2, and Grades 3-5 complications. An ordinal logistic regression model was constructed to assess the association between comorbidities, demographics, tumor characteristics, and surgical complications. Results In total, 448 patients met inclusion criteria. Perioperative mortality rate at 30 days was 1.6% (n = 7). The rate of severe complications (Clavien-Dindo 3 or higher) was 13.6% (n = 61). Multivariate analysis using an ordinal logistic regression model showed no association between Charlson comorbidity index score and Clavien-Dindo grade of postoperative complication. Advanced T-stage was significantly associated with complications (p = 0.0014; odds ratio: 3.442 [95% confidence interval: 1.615, 7.338]). Conclusion Surgery for sinonasal and skull base tumors is safe with a low mortality rate. Advanced T-stage is associated with postoperative complications. These findings have implications for preoperative risk stratification. Key Points Surgery for sinonasal malignancy is safe with a 30 mortality of 1.6% and rate of severe complications of 12.8%. There is no association between patient comorbidity and post operative complication. On multivariate analysis, only advanced T stage was associated with increased rate of surgical complication.

[Objective] Compare health-related quality of life (HRQoL) of selinexor versus placebo in patients with dedifferentiated liposarcoma., [Materials & methods] HRQoL was assessed at baseline and day 1 of each cycle using the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire. Results were reported from baseline to day 169 (where exposure to treatment was maximized while maintaining adequate sample size)., [Results] Pain scores worsened for placebo versus selinexor across all postbaseline visits, although differences in HRQoL at some visits were not significant. Other domains did not exhibit significant differences between arms; however, scores in both arms deteriorated over time., [Conclusion] Patients treated with selinexor reported lower rates and slower worsening of pain compared with patients who received placebo., This study was funded by Karyopharm Therapeutics, Inc. M Gounder: reports an institutional research grant from Karyopharm, personal fees from Karyopharm, Epizyme, Springworks, Daiichi, Bayer, Amgen, Tracon, Flatiron, Medscape, Physicians Education Resource, Guidepoint, GLG and UpToDate; and grants from the National Cancer Institute, National Institutes of Health (P30CA008748) – core grant (CCSG shared resources and core facility). ARA Razak: consulting/Ad board: Merck & Adaptimmune Research support: Karyopharm Therapeutics, Deciphera, Blueprint Medicines, Pfizer, Adaptimmune, Merck, Roche/Genentech, Bristol-Myers Squibb, Medimmune, Amgen, GSK, AbbVie, Iterion Therapeutics. AM Gilligan: employee of Karyopharm Therapeutics, Inc. H Leong: employee of Karyopharm Therapeutics, Inc. X Ma: employee of Karyopharm Therapeutics, Inc. N Somaiah: consultant for Deciphera, Blueprint, Bayer Research Support from Ascentage, Astra-Zeneca, Daiichi-Sankyo, Deciphera, Eli Lilly, Karyopharm and GSK. SP Chawla: consultant for Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research though Collaboration, Janssen, Advenchen Laboratories, Bayer, NKMax, InhibRx. Grants or contracts from Amgen, Roche, GlaxoSmithKline, Threshold Pharmaceuticals, CytRx Corporation, Ignyta, Immune Design, TRACON Pharma, Karyopharm Therapeutics, SARC: Sarcoma Alliance for Research though Collaboration, Janssen, Advenchen Laboratories, Bayer, InhibRx, NKMax. G Grignani: consultant for Eli Lilly, Novartis, Glaxo, Pharmamar, EISAI, Bayer, Merck. SM Schuetze: consultant – NanoCarrier, UpToDate. Research funding to institution – Adaptimmune, Amgen, Blueprint, Glaxo-SmithKline, Karyopharm. B Vincenzi: Consultant for Pharmamar Eisai, Lilly, Abbott, Novartis, Accord AJ Wagner: consultant for Daiichi-Sankyo, Deciphera, Eli Lilly, Epizyme, NovoCarrier, Mundipharma, and Research Support to My Institution from Aadi Bioscience, Daiichi-Sankyo, Deciphera, Eli Lilly, Karyopharm and Plexxikon. RL Jones: consultant for Adaptimmune, Athenex, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, Pharmamar, Springworks, Tracon, Upto Date. J Shah: employee of Karyopharm Therapeutics, Inc. S Shacham: employee of Karyopharm Therapeutics, Inc. M Kauffman: employee of Karyopharm Therapeutics, Inc. RF Riedel: ownership - Limbguard, LLC (Spouse); Institutional Clinical Research Support - AADi, AROG, Blueprint, Daiichi-Sankyo, Deciphera, Glaxo-SmithKline, Karyopharm, Ignyta, Immune Design, NanoCarrier, Oncternal, Philogen, Plexxikon, Roche, Springworks, Tracon; Consultant/Advisor - Bayer, Blueprint, Daiichi-Sankyo, Deciphera, Ignyta, NanoCarrier. S Attia: reports research funding from Desmoid Tumor Research Foundation and research funding to their institution from: AB Science, TRACON Pharma, Bayer, Novartis, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, BTG, PTC Therapeutics, GlaxoSmithKline, FORMA Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

In the United States of America (US), most departments of otorhinolaryngology head and neck surgery have been performing thyroid surgery for many years. In contrast to the US, thyroid surgery is still dominated by general surgeons in most European countries. In numerous university centers, there continues to be friction regarding thyroid surgery. The focus of this editorial is to demonstrate that there is objective data in the literature to suggest that otorhinolaryngologists with appropriate training in head and neck surgery are well suited to perform the entire spectrum of thyroid surgery. The question of who is qualified to perform thyroid surgery is not determined by the basic specialty certification of the surgeon-general or otolaryngology; rather it depends on the training, skill and experience in surgery of the neck, of post-surgical and post-irradiated necks, and of neighboring structures. ispartof: ADVANCES IN THERAPY vol:36 issue:10 pages:2541-2546 ispartof: location:United States status: published

Objective Polymorphous adenocarcinoma of salivary gland (PAC) is rare. Despite being described as a low risk histology, some patients develop regional and distant metastasis. More aggressive behavior has been attributed to a PAC subcategory called cribriform adenocarcinoma of minor salivary glands (CAMSG). We examined oncological outcomes of PAC. Patients and methods Fifty-seven patients with PAC were identified from an institutional database of 884 patients surgically treated for salivary gland malignancies from 1985 to 2015. Detailed histopathological analysis was performed. Survival outcomes were calculated using the Kaplan-Meier method. Factors predictive of recurrence were identified using the Cox proportional hazard method. Results Fifty-four (95%) had tumors of minor salivary gland origin; the most frequent location was the oral cavity in 41 (76%), specifically the hard palate in 32 (55%). Forty-six patients (81%) were clinical T1-T2; 3 (5%) had a clinically positive neck. Thirty-two patients (56%) were classified as PAC and 14 (25%) as CAMSG. Forty-four patients (77%) had surgery alone; 13 (23%) had surgery and postoperative radiotherapy. The 5- and 10-year overall survival and disease-specific survival were 88% and 79% and 98% and 94%, respectively (median follow up 84 [1–159] months); 5- and 10-year recurrence-free survival were 93% and 88%, respectively. Univariate analysis showed male sex, III/IV stage, and CASMG variant had increased incidence of recurrence but were not statistically significant. Conclusion PAC of the salivary glands is an indolent disease with good survival outcomes. Recurrence is uncommon and tends to occur late. Long-term follow-up is indicated in patients with this disease.

BACKGROUND We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC). METHODS Retrospective analysis of DOI (