Pretreatment weight status and weight loss among head and neck cancer patients receiving definitive concurrent chemoradiation therapy: implications for nutrition integrated treatment pathways.

PURPOSE: The purpose was to examine the effect of pretreatment weight status on loco-regional progression for patients with squamous cell carcinoma of the head and neck (SCCHN) after receiving definitive concurrent chemoradiation therapy (CCRT). METHODS: In an expanded cohort of 140 patients, we retrospectively reviewed weight status and loco-regional progression of SCCHN patients treated with CCRT between 2004 and 2010. RESULTS: Pretreatment ideal body weight percentage (IBW%) was statistically significantly different for patients with disease progression than for those without progression (p = 0.02) but was not an independent predictor of progression. Median pretreatment IBW% was 118 (72-193) for the progression-free group and was 101.5 (73-163) for the group with progression. Both groups suffered clinically severe weight loss of approximately 9 % from baseline to end treatment. CONCLUSIONS: Pretreatment weight status, a very crude indicator of nutrition status, may have prognostic value in patients with SCCHN undergoing definitive CCRT. Inadequate nutritional status in these patients has been associated with poor clinical outcomes and decreased quality of life. Based on this report and others, the best next steps include routine validated malnutrition screening and the testing of evidence-based nutrition care protocols with the goals of minimizing weight loss and improvement of quality of life.

Treatment patterns of malignant melanoma in the United States from 2011 to 2016: a retrospective cohort study.

Background: Since 2011, the approval of several new agents has improved treatment options for malignant melanoma. We describe treatment patterns for malignant melanoma in the United States from the MarketScan database from 2011 to 2016.Methods: Treatments used for patients aged >18 years diagnosed with malignant melanoma after January 1, 2011 and enrolled in the Truven MarketScan database were analyzed. Patient data were collected for the 12-month period from the date of the first melanoma diagnosis to either death, the pre-specified study end date (August 31, 2016), or date of termination of health insurance. Treatment patterns from 2011-2013 and 2014-2016 were analyzed according to agent, year of drug administration, and line of therapy.Results: From 2011 to 2016, use of cytokines (63.8; 13.3%) and chemotherapy (19.6; 12.9%) decreased, and use of checkpoint inhibitors increased (2.0; 49.9%). Checkpoint inhibitor use also increased across all lines of therapy from 2011-2013 and 2014-2016. Use of BRAF/MEK inhibitors remained relatively stable from 2011 to 2016 (6.5-12.5%); however, the use of vemurafenib monotherapy decreased (6.5; 0.8%), and treatment with combination regimens increased (0; 10.9%) from 2011-2016. BRAF/MEK inhibitor use only increased in the first line setting from 2011-2013 (9.7%) to 2014-2016 (11.2%).Conclusion: With the approval of immune checkpoint inhibitors, BRAF/MEK inhibitors, and targeted therapies, the therapeutic landscape for the treatment of metastatic melanoma has shifted dramatically away from cytokines and chemotherapy. Treatment patterns will likely continue to evolve as scientific advances are made.

Open-Label, phase 2 study of blinatumomab as second salvage therapy in adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.

The phase 2 portion of this open-label phase 2/3 study assessed the efficacy and safety of blinatumomab as second salvage for aggressive relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL) following platinum-based first salvage chemotherapy. Forty-one patients with aggressive disease (32% relapsed; 68% refractory) enrolled and received stepwise blinatumomab (9-28-112 µg/day) in a 70-day cycle 1 and an optional 28-day cycle 2; 19 (46%) completed cycle 1 and 3 (7%) completed cycle 2. The overall response rate after 12 weeks was 37%, including 9 (22%) complete metabolic responses. Eight (20%) patients (all responders) subsequently received stem cell transplants. Grade ≥3 adverse events were reported in 29 (71%) patients. Grade 3 cytokine release syndrome occurred in one patient. Grade 3 neurologic events occurred in 10 (24%) patients; all resolved. Blinatumomab monotherapy appears effective as second salvage therapy in patients with r/r aggressive B-NHL. Trial registration: NCT02910063.

Treatment patterns of melanoma by BRAF mutation status in the USA from 2011 to 2017: a retrospective cohort study.

AIM: To describe treatment changes from 2011 to 2017 and demographic/clinical characteristics of patients with advanced melanoma who received systemic therapy by BRAF status. PATIENTS & METHODS: Treatment patterns were evaluated in adults from the Oncology Services Comprehensive Electronic Records database who received antimelanoma systemic therapy. RESULTS: Checkpoint inhibitors were prevailingly prescribed (66%); usage increased from 2011 (21%) to 2017 (84%). BRAF/MEK inhibitors were the second most common (21%); usage increased from 2011 (6%) to 2012 (18%) and stabilized until 2017 (22%). BRAF/MEK inhibitors (65%) and checkpoint inhibitors (57%) were predominantly used for BRAFMut melanoma. CONCLUSION: Overall, checkpoint inhibitors have supplanted other therapies for advanced melanoma. Treatment shifts have occurred for BRAFMut melanoma, notably increased use of checkpoint inhibitors and BRAF/MEK combinations compared with monotherapies.

Clinicians' Perspectives on Cure in Adult Patients with Acute Lymphoblastic Leukemia with Minimal Residual Disease: A Delphi Study.

Hematologic complete remission (CR) is achievable for most adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL). However, minimal residual disease (MRD) in patients with hematologic CR is associated with increased risk of relapse, shorter survival, and poorer transplantation outcomes. This study explored the concept of cure in adults with Philadelphia chromosome-negative (Ph-) BCP-ALL by MRD status at first hematologic CR (CR1) to inform evaluation of the clinical and economic benefits of new agents, where the concept of cure is important but long-term data are not available. The study used modified Delphi methodology involving clinicians experienced in the treatment of adult ALL. Participants completed a questionnaire, which was followed by country-specific panel discussions to discuss results and identify consensus on concepts and definitions. Clinicians from France (n = 4), Germany (n = 4), and the UK (n = 5) took part. Participants described cure in terms of the probability of future relapse. Relapse-free survival (RFS) was the preferred outcome measure to describe cure for the three patient groups considered (patients with MRD at CR1; patients who become negative for MRD after further treatment; patients who continue to have MRD). Consensus was reached on definitions of cure: that cure would begin to be considered at 3 years' RFS and/or would be highly likely at 5 years' RFS. Participants agreed that patients with MRD should usually undergo hematopoietic stem cell transplantation to have the best chance of survival; consensus was reached that alternatives are required when transplantation is not an option. Panels agreed that patients who achieve cure have a higher mortality rate and lower health-related quality of life than the general population. This study provides quantitative and qualitative information on the concept of cure in Ph- BCP-ALL in CR by MRD status applicable to interpreting the value of new therapies.Funding: Amgen.Plain Language Summary: Plain language summary available for this article.

Observational study of talimogene laherparepvec use for melanoma in clinical practice in the United States (COSMUS-1).

AIM: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice. MATERIALS & METHODS: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible. RESULTS: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported. CONCLUSION: T-VEC was well tolerated and showed clinical utility.

Combined surgery and radiation improves survival of tonsil squamous cell cancers.

OBJECTIVE: The study evaluated the addition of surgery (S) to radiation (RT) on survival of squamous cell carcinomas (SCC) of tonsillar-fossa (TF) in a modern cohort with similar epidemiology and treatment as current patients. STUDY DESIGN: Retrospective analysis utilizing Surveillance, Epidemiology, and End Results (SEER) Program data. RESULTS: For all stages combined TF patients who received S+RT had superior OS (p < 0.01) and DSS (p < 0.01). For each stage OS and DSS was superior for S+RT (p < 0.05). In multivariate analysis, HRs for OS were statistically significantly higher for TF patients (stage 2, 3, and 4) receiving RT alone (p < 0.001). MATERIALS AND METHODS: TF SCC patients treated with either S+RT or RT alone between 2004 and 2011 were examined (n = 6,476). Primary outcome measures included overall survival (OS) and disease specific survival (DSS). Cox proportional hazard ratios (HR) were estimated for patients treated with S+RT compared to RT alone. CONCLUSIONS: OS and DSS were superior for all stages combined and for stages 2, 3, and 4 in TF patients who received S+RT compared to RT alone.

Subsite variation in survival of oropharyngeal squamous cell carcinomas 2004 to 2011.

OBJECTIVES/HYPOTHESIS: To evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors. STUDY DESIGN: Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011. METHODS: The cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival. RESULTS: The cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa. CONCLUSIONS: In this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1087-1092, 2017.

Smoking cessation is associated with improved survival in oropharynx cancer treated by chemoradiation.

OBJECTIVES/HYPOTHESIS: The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN: Retrospective review. METHODS: Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS: Of 120 evaluable patients, 71% had HPV+ tumors. Median follow-up duration for the entire cohort was 41.5 months (range = 6-88 months). HPV+ current smokers experienced significantly worse 5-year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV- current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35-10.0). Similarly, current smokers with HPV- tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS: Current smoking is associated with poor prognosis, independent of HPV status, in CCRT-treated OPSCC patients. Current smoking produced an approximately four- to sevenfold increase in risk of mortality for HPV+ and HPV- patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2733-2738, 2016.

Survival differences between organ preservation surgery and definitive radiotherapy in early supraglottic squamous cell carcinoma.

OBJECTIVE: Single-modality treatment, either with organ preservation surgery (OPS) or definitive radiation (RT), is the treatment of choice for patients with early supraglottic squamous cell carcinoma (SGC). However, studies comparing the effectiveness of these 2 techniques are lacking. This study compares the survival outcomes in early SGC patients treated with OPS versus RT. STUDY DESIGN: Secondary data analysis. SETTING: Surveillance, Epidemiology and End Results database. SUBJECTS AND METHODS: This study included adult patients with early-stage (T1N0, T2N0) SGC undergoing single-modality treatment with either OPS (with or without neck dissection [ND]) or RT between 1988 and 2008. Survival analysis was used to compare the overall survival (OS) and disease-specific survival (DSS) between patients treated with OPS+ND, OPS alone, and RT. RESULTS: A total of 2631 T1/T2 N0 SGC patients were identified, of whom 167 (6%) were treated with OPS+ND, 186 (7%) with OPS only, and 2278 patients (87%) with definitive RT only. In stage I (T1N0) SGC patients, a significantly better 5-year DSS was noted for both OPS+ND (81% vs 68%, hazard ratio [HR] = 0.61, P = .03) and OPS only (82% vs 68%, HR = 0.70, P = .05) when compared with definitive RT. For stage II (T2N0) patients, only OPS+ND resulted in a significantly better 5-year DSS (86% vs 60%, HR = 0.31, P < .001) when compared with patients treated with RT. CONCLUSIONS: Patients with early SGC who underwent OPS+ND had better OS and DSS than patients undergoing RT alone. OPS+ND may be considered a viable and preferred treatment option in these patients.

Survival rates and prognostic factors for infiltrating salivary duct carcinoma: Analysis of 228 cases from the Surveillance, Epidemiology, and End Results database.

BACKGROUND: The survival rates and prognostic factors for salivary duct carcinoma (SDC) are not clear. METHODS: Survival estimates and prognostic factors were evaluated for 228 patients with SDC identified from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Median overall survival (OS) duration for patients with SDC was 79 months and 5-year disease-specific survival (DSS) rate was 64%. Among patients with SDC with lymph node involvement, larger primary tumor size (>3 cm) was associated with twice the risk of death (p < .03). Factors predictive of improved DSS were age (p = .01), tumor size (p = .006), tumor grade (p = .02), and lymph node involvement (p < .001). Adjuvant radiotherapy did not improve survival when compared to surgery alone for early-stage (I-II) disease (p = .28). CONCLUSION: Younger patients with SDC (<50 years) showed a better prognosis. Primary tumor size and lymph node involvement were independent and additive risk factors for poor prognosis. The role of adjuvant radiotherapy in the treatment of SDC needs to be explored further.

Sentinel node biopsy in lieu of neck dissection for staging oral cancer.

IMPORTANCE: Neck dissection is the standard staging procedure to ascertain the pathologic status of cervical lymph nodes in patients with oral cavity squamous cell carcinoma (OSCC), but it results in multiple morbidities. OBJECTIVE: To examine outcomes of patients with OSCC who underwent sentinel node biopsy (SNB) as the sole neck staging procedure. DESIGN: Retrospective review of patients who underwent SNB during the period 2005 through 2011. SETTING: National Cancer Institute­designated comprehensive cancer center. PARTICIPANTS: Thirty-eight patients with clinically T1 or T2N0 OSCC. INTERVENTIONS: Preoperative lymphoscintigraphy with intraoperative gamma probe localization was used. Sentinel lymph nodes were serially sectioned, formalin fixed, and examined at 3 levels. All patients with positive SNB results underwent neck dissection, and the patients with negative SNB results were observed clinically. MAIN OUTCOMES AND MEASURES: Sensitivity and predictive value of SNB, recurrence rates, and disease-specific survival rates. RESULTS: There were 18 T1 and 20 T2 tumors. Five patients had positive SNB results, of whom 3 had additional positive nodes on subsequent neck dissection. Two of 33 patients with negative SNB results developed a regional recurrence. The sensitivity and negative predictive value for staging the neck with SNB alone were 71% (5 of 7) and 94% (31 of 33), respectively. Mean follow-up was 31 months. The mean disease-free survival duration for patients with positive and negative SNB results was 30 and 65 months, respectively (P = .08). The disease-specific survival rate for patients with positive and negative SNB results was 80% and 91%, respectively. There was no significant difference in disease-specific survival between patients with true-negative and false-negative SNB results (34 vs 44 months; P = .38). CONCLUSIONS AND RELEVANCE: The majority of patients with positive results on SNB had additional positive nodes on neck dissection. A low rate of isolated neck recurrence was found in patients with negative results on SNB. Individuals with negative results on SNB exhibited better overall and disease-specific survival than those with positive results.

Palatal reconstruction.

PURPOSE OF REVIEW: The palate is a critical structure, playing pivotal roles in speech, swallowing, and mastication. Reconstruction of the palate is among the most difficult challenges faced by head and neck reconstructive surgeons. The primary aims of this review are to catalog the evolution of the classification systems for palatal defects, discuss decision making surrounding the various options for hard palate reconstruction, and address the special challenges and techniques involved in soft palate reconstruction. RECENT FINDINGS: The Okay Classification System has become the standard by which most hard palatal defects are assessed. Free tissue transfer seems to be becoming an increasingly important therapeutic modality for many hard and soft palate defects. SUMMARY: Success in the management of palatal defects depends on accurate appreciation of the size and functional extent of each defect, careful patient selection, and specific attention to each patient's goals.

Determining the protein drug release characteristics and cell adhesion to a PLLA or PLGA biodegradable polymer membrane.

Biodegradable polymers are of interest for developing controlled protein drug delivery platforms. In this study, two poly (alpha-hydroxy) esters were formulated with Aerosol-OT, a surfactant stabilizer, to encapsulate the protein keratinocyte growth factor (KGF) for controlled release KGF is involved in a number of crucial biologic processes, most notably epithelial growth and repair. The concentration of KGF that caused a biological response in vitro was determined (optimally 10 ng/mL) and compared with the release of KGF from the two biodegradable polymer membrane formulations. Each polymer formulation released biologically relevant levels, 10 ng/mL of active KGF, although with different times release kinetics. The membrane composed of PLGA/AOT/KGF exhibited a faster release rate of KGF into solution after 120 h of degradation time than the release rate of the PLLA/AOT/KGF matrices. Cell seeding assays showed that both polymer matrices, when formulated with AOT, sustained cell growth. Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) was used to characterize the distribution of AOT and KGF through the polymer membrane. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Oropharyngeal cancer: current understanding and management.

PURPOSE OF REVIEW: The goals of this article are: to briefly review oropharyngeal anatomy; to provide a review of the epidemiology of oropharyngeal cancer in the Western Hemisphere; to review the literature on the association of human papilloma virus with oropharyngeal cancer; to review the recent literature on evolving diagnostic techniques for oropharyngeal cancer; and to summarize accepted management strategies for oropharyngeal cancer by subsite. RECENT FINDINGS: The incidence of oropharyngeal cancer may be increasing among younger age groups in the Western Hemisphere, and this may be related to an increased association with human papillomavirus 16. The implications of this viral association with regard to outcomes and management strategies remain under investigation. Screening with toluidine blue, autofluorescence, or both may be useful adjuncts to physical examination and panendoscopy in assessing potentially invasive or dysplastic lesions of the oropharynx. These techniques remain under study. MRI and PET scan are proving to be useful techniques for assessing local extension, regional metastases, and recurrences of squamous cell carcinoma (SCC) of the oropharynx in selected cases. However, serial computed tomography scanning remains the imaging modality of choice in the United States. Early SCCs of the oropharynx (T1-2), in general, may be managed effectively with either surgery or primary irradiation, though, with either technique, clinicians must have a management plan for the neck. Advanced SCCs of the oropharynx (T3-4, nodally aggressive, or both) require multimodal approaches consisting of either surgery along with adjuvant irradiation or concurrent chemoradiation along with salvage surgery (as necessary). SUMMARY: Management of SCC of the oropharynx is in a period of transition because of evolving changes in our understanding of the oncogenic process; evolving diagnostic techniques; and evolving combinations of therapies, both surgical and nonsurgical. For the time being, we propose using local subsite and disease stage to guide therapeutic decision-making.