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Purpose To present evidence-based guidelines for the treatment of oropharyngeal squamous cell carcinoma (OPSCC) with definitive or adjuvant radiation therapy (RT). Methods and materials The American Society for Radiation Oncology convened the OPSCC Guideline Panel to perform a systematic literature review investigating the following key questions: (1) When is it appropriate to add systemic therapy to definitive RT in the treatment of OPSCC? (2) When is it appropriate to deliver postoperative RT with and without systemic therapy following primary surgery for OPSCC? (3) When is it appropriate to use induction chemotherapy in the treatment of OPSCC? (4) What are the appropriate dose, fractionation, and volume regimens with and without systemic therapy in the treatment of OPSCC? Results Patients with stage IV and stage T3 N0-1 OPSCC treated with definitive RT should receive concurrent high-dose intermittent cisplatin. Patients receiving adjuvant RT following surgical resection for positive surgical margins or extracapsular extension should be treated with concurrent high-dose intermittent cisplatin, and individuals with these risk factors who are intolerant of cisplatin should not routinely receive adjuvant concurrent systemic therapy. Induction chemotherapy should not be routinely delivered to patients with OPSCC. For patients with stage IV and stage T3 N0-1 OPSCC ineligible for concurrent chemoradiation therapy, altered fractionation RT should be used. Conclusion The successful management of OPSCC requires the collaboration of radiation, medical, and surgical oncologists. When high-level data are absent for clinical decision-making, treatment recommendations should incorporate patient values and preferences to arrive at the optimal therapeutic approach. [ABSTRACT FROM AUTHOR]

Purpose: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT.Methods: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks.Results: Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT.Conclusions: SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon. [ABSTRACT FROM AUTHOR]

Definitive chemoradiation therapy has evolved as the preferred organ preservation strategy in the treatment of locally advanced head-and-neck cancer (LA-HNC). Dry mouth and dysphagia are among the most common and most debilitating treatment-related toxicities that frequently necessitate the placement of enteral feeding tubes (FT) in these patients to help them meet their nutritional requirements. The use of either a percutaneous endoscopic gastrostomy tube or a nasogastric tube, the choice of using a prophylactic vs a reactive approach, and the effects of FTs on weight loss, hospitalization, quality of life, and long-term functional outcomes are areas of continued controversy. Considerable variations in practice patterns exist in the United States and abroad. This critical review synthesizes the current data for the use of enteral FTs in this patient population and clarifies the relative advantages of different types of FTs and the timing of their use. Recent developments in the biologic understanding and treatment approaches for LA-HNC appear to be favorably impacting the frequency and severity of treatment-related dysphagia and may reduce the need for enteral tube feeding in the future. [Copyright &y& Elsevier]

The salivary gland cancers are uncommon neoplasms of the head and neck, which exhibit considerable pathologic, biological, and clinical diversity. Surgical resection, often with postoperative radiation, is the standard therapeutic approach, and the results after treatment vary widely depending on the tumor histology. Chemotherapy has been of only limited palliative benefit in patients with advanced disease, and there has been little exploration of its use in definitive management. Recent investigation has focused on identification of the characteristic molecular signatures and genomic alterations of the specific histologic subtypes. These efforts have suggested the potential for molecularly targeted therapies, and clinical trials exploring this approach are currently underway. [Copyright &y& Elsevier]

Objective: The objective of the study is to examine the utility of positron emission tomography (PET) for staging and restaging after treatment of paranasal sinus carcinomas. Study Design: Retrospective data review was done. Subjects and Methods: Patients selected underwent PET for sinonasal neoplasms from 2003 to 2008 at a tertiary care referral center. Results: Seventy-seven scans were reviewed from 31 patients. The pathologies included olfactory neuroblastoma (n = 9), squamous cell carcinoma (n = 6), sinonasal undifferentiated carcinoma (n = 6), sinonasal melanoma (n = 6), and minor salivary gland carcinomas (n = 4). The positive predictive value of studies performed for restaging at the primary, neck, and distant sites were 56%, 54%, and 63%; negative predictive values were 93%, 100%, and 98%, respectively. During restaging, 32% of patients were accurately upstaged secondary to neck or distant site involvement. Conclusion: Positron emission tomography serves as a useful adjunct to conventional imaging in the management of sinonasal malignancies. Negative studies are effective in predicting absence of disease as seen in the consistently high-negative predictive values. Positive studies need to be viewed cautiously given the high rate of false-positive studies. When viewed in conjunction with clinical examination, endoscopic assessment, and focused biopsies, they may effectively result in a more accurate assessment of the extent of disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: T1 and T2 tonsillar squamous cell cancer with limited neck disease can be managed with single-modality radiation or surgery. Over 11 years, 17 patients underwent radical tonsillectomies; and 33 patients underwent radiation-based treatments for T1 and T2 and N0 to N2a tonsil cancer. Patients were intended to receive single-modality treatment based on presentation; however, some ultimately received adjuvant treatments. Methods: A retrospective chart review to compare overall survival (OS), disease-specific survival (DSS), and locoregional control (LRC) between the groups was used. Results: In surgical group, of 17 patients, 11 underwent surgery alone, 3 underwent surgery and radiation, and 3 underwent surgery with concurrent chemoradiation. Five-year OS for the surgical and radiation groups was 93% and 72%, respectively (no significance achieved). Five-year DSS rates (93% and 80%) and LRC (69% and 89%) similarly did not yield any significant difference. Conclusion: Surgery remains a viable option in the management of T1 and T2 tonsillar cancers with comparable LRC, OS, and DSS. [Copyright &y& Elsevier]

Objective: The study objective was to develop a treatment algorithm for cT2N0M0 esophageal cancer by determining (1) errors in clinical staging and (2) consequences of overtreatment and undertreatment of incorrectly clinically staged patients. Methods: Of 742 clinically staged patients, 61 (8.2%) had cT2N0M0 cancer; 45 underwent surgery alone; 8 underwent surgery and postoperative adjuvant therapy; and 8 underwent induction therapy, then surgery. As reference, 31 of 666 patients (4.7%) who underwent surgery first had pT2N0M0 cancer and a 5-year survival of 61% ± 9.3%. Referent values were calculated from 445 clinically staged patients who underwent surgery first. Unmatched and matched survival comparisons were made using the log-rank test. Results: Only 7 of 53 cT2N0M0 cancers treated with surgery first were pT2N0M0 (13% positive predictive value). Of incorrectly staged cT2N0M0 cancers (46/53), 29 (63%) were overstaged and 17 (37%) were understaged. Most overstaged cancers were pT1 (11 [38%] T1a and 15 [52%] T1b), and most understaged cancers were pN1 (13 [76%]). Matched overstaged patients treated by surgery alone (25/28) had a 5-year survival similar to that of patients with pTNM (69% ± 9.8% vs 63% ± 13%, P =.8). Understaged patients did better at 5 years than patients with pTNM if they had postoperative adjuvant therapy, not surgery alone (43% ± 22% vs 10% ± 9.5%, P = .17). Induction therapy decreased 5-year survival compared with all other treatment strategies (13% ± 12% vs 52% ± 7.4%, P =.05). Conclusions: Patients with cT2N0M0 cancers should undergo surgery first with lymphadenectomy. Clinically understaged patients should receive postoperative adjuvant therapy. In the unlikely event that patients with cT2N0M0 cancers are found to have an uncommon pT2N0M0 cancer, they will have acceptable survival with surgery alone. [Copyright &y& Elsevier]

Purpose: The Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. Methods and Materials: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Results: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3–40.3 months). Median age was 65 (range, 42–85 years). Median KPS was 70 (range, 40–100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Conclusions: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons. [Copyright &y& Elsevier]

Background: Brain metastases from esophageal cancers are uncommon, yet our impression was that they occurred more frequently than expected after esophagectomy plus adjuvant therapy. Therefore, we determined (1) incidence and prevalence of, risk factors for, and survival after development of brain metastases following esophagectomy for esophageal cancer, and (2) their association with adjuvant therapy. Methods: From 1985 to 2002, 403 patients (52%) underwent esophagectomy alone and 369 esophagectomy plus adjuvant therapy (118 [15%] preoperative only, 124 [16%] postoperative only, and 127 [16%] both). Hazard-function methodology was used to characterize time-related occurrence of brain metastases and risk factors. Inferences were confirmed by propensity analysis. Results: Twenty-nine patients developed brain metastases, 20 within 1 year; 6 had undergone surgery alone, and 23 had adjuvant therapy. Prevalence was 2.5% 5 years after surgery alone, but 8.4%, 7.0%, and 18.4% after preoperative adjuvant therapy only, postoperative adjuvant therapy only, and both, respectively (p < 0.0001). Greater number of locoregional lymph node metastases was associated with brain metastases after surgery alone (p = 0.04). Distant metastases (p = 0.03) and both preoperative and postoperative adjuvant therapy (p = 0.004) were risk factors. Median survival after diagnosis of brain metastases was 3.5 months. Postesophagectomy propensity-matched survival was shorter after adjuvant therapy than after surgery alone; thus, time available for developing brain metastases after surgery alone was slightly lower. Conclusions: A dose-related increased incidence of brain metastases after adjuvant therapy for esophageal cancer cannot be explained by increased longevity. Adjuvant therapy itself, not just advanced disease, appears to create conditions conducive to developing these rapidly fatal metastases. [Copyright &y& Elsevier]

The low surgical cure rate in patients with stage III non-small cell lung cancer has prompted an exploration of multimodality treatment strategies. Mature results are presented from a phase II trial of accelerated hyperfractionated radiation therapy, concurrent paclitaxel/cisplatin chemotherapy and surgery for these patients. Between 1994 and 1997, 45 patients with surgically demonstrated stage III non-small cell lung cancer underwent induction treatment with a 96 h continuous cisplatin infusion (20 mg/m2 per day) and a 24 h infusion of paclitaxel (175 mg/m2) given concurrently with accelerated hyperfractionated radiation therapy (1.5 Gy twice daily) to a total dose of 30 Gy. Induction was completed in ten treatment (12 total) days. Surgical resection was scheduled 4 weeks later with a second identical course of chemoradiotherapy given 4–6 weeks post-operatively, to a total radiation dose of 60–63 Gy. Thirty-five patients had stage IIIA disease and ten had stage IIIB disease (eight with N3 tumors). Induction toxicity included nausea in 89%, dysphagia in 89%, and neutropenia <1000/mm3 in 84% which required hospitalization for fever in 40%. There were no toxic deaths during induction. About 40 of the 45 patients (89%) were operable and 32 (71%) were resectable for cure. A pathologic response was identified in 22 patients (49%); five patients (11%) had no residual disease. Fourteen patients (31%) were downstaged to mediastinal node negativity. With a median follow-up of 60 months, the Kaplan–Meier projected 5-year overall survival was 29%; locoregional control 79%; and distant metastatic disease control 38%. The projected 5-year survival for the 14 patients downstaged to mediastinal node negativity was 50%. For the 19 patients with residual ipsilateral mediastinal node involvement at surgery it was 32%. This short-course of paclitaxel and cisplatin chemotherapy and concurrent accelerated fractionation radiation is tolerable despite significant myelosuppression. Locoregional control is excellent and survival is better than historical expectations. Patients downstaged to mediastinal node negativity have a prognosis similar to those with de novo stage IB and II disease. Distant metastases are the major cause of treatment failure. [Copyright &y& Elsevier]

The treatment of locally advanced oral cavity cancer is often multimodal, involving surgical resection, radiotherapy (RT), and chemotherapy. Systemic therapy is the mainstay of treatment for recurrent/metastatic disease. While the concurrent use of cisplatin with post-operative RT is well established in patients with high risk features of extranodal extension and/or positive surgical margins following resection, the role of chemotherapy in other curative settings is not clear. Studies reporting success of induction chemotherapy or definitive chemoradiotherapy in absence of primary resection include all anatomic sites of head and neck cancer, and oral cavity cancer subset is rarely reported as a separate analysis, thus limiting the interpretation of results. This article will focus on the use of systemic therapy for locoregionally advanced oral cavity cancer. [ABSTRACT FROM AUTHOR]

Objective: Nivolumab is the first drug to demonstrate a survival benefit for platinum-refractory recurrent or metastatic head and neck cancer. We performed a cost-utility analysis to assess the economic value of nivolumab as compared to alternative standard agents in this context.Materials and Methods: Using data from the CheckMate 141 trial, we constructed a Markov simulation model from the US payer's perspective to evaluate the cost-effectiveness of nivolumab compared to physician choice of either cetuximab, methotrexate or docetaxel. Alternative strategies considered included: single-agent cetuximab, methotrexate or docetaxel, or first testing for PD-L1 to select for nivolumab. Costs were extracted from Medicare and utilities from the literature and CheckMate. Probabilistic sensitivity analysis (PSA) was used to evaluate parameter uncertainty. $100,000/QALY was the primary threshold for cost-effectiveness.Results: When comparing nivolumab to the standard arm of CheckMate, nivolumab demonstrated an incremental cost-effectiveness ratio (ICER) of $140,672/QALY. When comparing standard therapies, methotrexate was the most cost-effective with similar results for docetaxel. Nivolumab was cost-effective compared to single-agent cetuximab (ICER $89,786/QALY). Treatment selection by PD-L1 immunohistochemistry did not markedly improve the cost-effectiveness of nivolumab. Factors likely to positively impact the cost-effectiveness of nivolumab include better baseline quality-of-life, poor tolerability of standard treatments and/or a lower cost of nivolumab.Conclusions: Nivolumab is preferred to single-agent cetuximab but requires a willingness-to-pay of at least $150,000/QALY to be considered cost-effective when compared to docetaxel or methotrexate. Selection by PD-L1 does not markedly improve the cost-effectiveness of nivolumab. This informs patient selection and clinical care-path development. [ABSTRACT FROM AUTHOR]

Summary: Chemotherapy has assumed an important role in multidisciplinary management of patients with head and neck cancer. Much recent progress is attributable to successful design and careful implementation of clinical trials. In addition to showing the efficacy of chemotherapy, trials also instruct about how to improve experimental design so that we can make the most of what is learned. In this Personal View, several important studies in head and neck cancer are reviewed, with focus on issues raised by their design, potential solutions to these difficulties, and challenges that future investigations of this disease will face. [ABSTRACT FROM AUTHOR]

Purpose: To determine the patterns of adjuvant chemoradiotherapy use in elderly patients treated with definitive surgical resection for squamous cell carcinoma of the head and neck with extracapsular extension (ECE) or positive margins and determine whether an association with overall survival (OS) exists with adjuvant concurrent chemoradiotherapy (CRT).Methods and Materials: The National Cancer Database was queried to identify patients with SCC of the oral cavity, oropharynx, larynx, and hypopharynx who were treated with primary definitive surgery and adjuvant radiation therapy between 2004 and 2012. For elderly patients (aged >70 years) with pathology revealing ECE or positive margin, the benefit of concurrent chemotherapy was explored using multivariable Cox proportional hazards modeling.Results: A total of 7349 patients were identified meeting study criteria, of whom 1187 were elderly (aged >70 years) with a median follow-up of 30.6 months. Of these elderly patients, 445 had ECE or positive margin and represent the study population, of whom 187 (42%) received CRT. Delivery of CRT in this cohort increased over the study period, and intensity modulated radiation therapy was associated with increased use of CRT (odds ratio 2.07; P=.004). Increasing age was associated with reduced use of CRT (odds ratio 0.88; P<.001). Chemoradiotherapy was associated with a significant improvement in OS on multivariable analysis (hazard ratio 0.74; P=.04) and a trend toward significance on inverse propensity score analysis (hazard ratio 0.78; P=.051). Three-year OS was 53.8% in the CRT group, compared with 44.6% in the adjuvant radiation therapy-alone patients.Conclusions: The use of adjuvant CRT is increasing among elderly patients with resected squamous cell carcinoma of the head and neck exhibiting ECE or positive margins. Chemoradiotherapy was associated with an improvement in OS on multivariable analysis but not propensity-weighted analysis. Among fit elderly patients with ECE or positive margins after definitive surgical resection, concurrent chemotherapy can be carefully considered. [ABSTRACT FROM AUTHOR]

Objectives: To analyze a cohort of patients with HPV positive, oropharyngeal squamous cell carcinoma (OPSCC) treated with lower radiation dose to clinically involved lymph nodes.Materials and Methods: We retrospectively identified patients with HPV positive, OPSCC treated with definitive chemoradiotherapy (70-74.4Gy) to the primary site and, since a post-radiation neck dissection was planned, 54Gy to the involved nodal areas. Neck dissection was ultimately omitted in all cases due to complete response. All patients were treated with a 3 field approach with sequential boost plans. Composite plans were generated retrospectively and primary tumor and lymph node GTVs were contoured and nodes were expanded by 5mm to form a CTV. Mean dose, dose to 95% (D95) and dose to 99% (D99) were determined.Results: Fifty patients treated from 2008 to 2010 with 113 involved nodes were identified. The median age was 57years, and 6%, 46%, and 48% were current, former, and never smokers. Ninety percent of patients received concurrent cisplatin based chemotherapy. Median D95 and D99 to involved nodes were 59.8Gy and 55.9Gy respectively. At a median follow up of 54.1months, two patients developed nodal failure and four developed metastatic disease. Five year loco-regional control, disease free survival and overall survival were 96%, 81% and 86% respectively.Conclusion: In this exploratory analysis, regional lymph node control in HPV positive oropharyngeal cancer was not compromised by dose de-escalated radiotherapy to involved nodes in the setting of concurrent cisplatin based chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT).Materials and Methods: We queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival.Results: We identified 187 cases: median age 58 (range, 24-87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63-162 days). OS was worse for TPT > 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT > 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1-1.28]; P = 0.043), perineural invasion, age and positive LN (p < 0.05 for all).Conclusion: In one of the largest multi-institutional cohorts, TPT > 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether gender and race influence survival in non–small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0–122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival. [Copyright &y& Elsevier]

Purpose: Mediastinoscopy is routinely carried out on the majority of nonmetastatic, non–small-cell lung cancer (NSCLC) patients in our institution. We used the results of mediastinoscopy from a Stage III NSCLC cohort to assess the reliability of positron emission tomography (PET) scans at identifying involved mediastinal lymph nodes (MLN) when used during radiotherapy planning. Methods and Materials: Mediastinoscopy was the gold standard. Characteristics of PET were calculated for nodal sensitivity. To compare the impact on contouring, theoretical nodal targets (NTs) containing involved MLNs were generated using PET and mediastinoscopy. We determined whether the NT derived from PET (NT-P) was equivalent to, greater than, or less than that seen with the mediastinoscopy (NT-M). Results: Data for 122 patients with Stage III NSCLC, treated between 2000 and 2004, were analyzed. After exclusions, 87 patients with Stage III disease by mediastinoscopy were analyzed. Overall PET sensitivity was 61% and positive predictive value was 94%. Of the 87 patients, 33 (38%) had no abnormal MLN findings by PET. Of 36 Stage IIIA cancer patients, 18 (50%) had NT-P equivalent to NT-M, 10 (28%) had smaller NT-Ps, and 8 (22%) had larger NT-Ps compared with NT-Ms. Of 18 Stage IIIB cancer patients, NTs were equivalent in 6 (34%); in 1 patient (5%) NT-P was larger than the corresponding NT-M, and in 11 (61%) smaller than the corresponding NT-M. Conclusions: In this study PET had modest sensitivity to detect MLN involvement and underestimated the extent of involved nodes for target definition. The role of PET in mediastinal contouring needs to be evaluated prospectively and ideally correlated with a pathology standard. [Copyright &y& Elsevier]

Summary: Purpose: The purpose of this open-label phase II SWOG study was to evaluate the activity of gemcitabine (Gemzar®; Eli Lilly, Indiana, USA) and cisplatin combination therapy, in patients with unresectable malignant mesothelioma of the pleura. Patients and methods: Fifty eligible chemotherapy naïve patients with histologically proven malignant mesothelioma of the pleura, and a SWOG performance status 0–2 were enrolled between February 1999 and August 2000. Treatment consisted of gemcitabine 1000mg/m2 and cisplatin 30mg/m2 on days 1, 8 and 15 of a 28-day cycle, until progression of disease or two cycles beyond complete response. Results: Using SWOG response criteria, one patient had a confirmed complete response and five patients had a confirmed partial response, for a total response rate of 12% (95% CI 5–24%). All the responses were seen in patients with epithelioid or unspecified histology. Stable disease was seen in 25 patients (50%). The median overall survival was 10 months (95% CI 7–15 months), with a median progression-free survival of 6 months. Sixteen patients experienced Grade 4 toxicity. Twelve of these Grade 4 toxicities were hematologic. There were no treatment-related deaths. Conclusions: Cisplatin–gemcitabine combination chemotherapy has modest activity with an acceptable toxicity profile, as first line treatment for patients with malignant mesothelioma. [Copyright &y& Elsevier]

Introduction: The objective of this study is to evaluate locoregional and distant failure for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) using American Joint Committee on Cancer eighth edition (AJCC 8) staging.Materials and Methods: Retrospective cohort study of 457 patients with HPV + OPSCC, treated with platinum-based chemoradiation from 2002 to 2018, followed for a median of 4.3 years. Time to locoregional failure (TTLRF) and distant failure (TTDF) were estimated by Kaplan-Meier method. Log-rank, recursive partitioning analysis (RPA), and multivariable Cox proportional hazards were used to evaluate associated factors and stratify risk.Results: Rates of five-year locoregional control (LRC) and distant control (DC) were 92% (95% CI, 90-95%) and 89% (95% CI, 85-92%), respectively. Smoking, T4, N3, and stage III were associated with significantly worse TTLRF. RPA identified three distinct locoregional failure groups: cT1-3 and <19 pack-years vs. cT1-3 with ≥19 pack-years vs. cT4 (five-year LRC: 97% vs. 90% vs. 82%, P < .0001). The only factor associated with significantly worse TTDF was smoking status, while stage was not correlated. RPA identified two prognostic groups: former or never smokers vs. current smokers (five-year DC: 92% vs. 77%, P = .0003).Discussion: In the largest evaluation of HPV + OPSCC after platinum-based chemoradiation using AJCC 8, risk for locoregional recurrence was stratified by smoking, T category, N category, and overall stage. Risk of distant recurrence was only stratified by smoking status and not related to stage. This has implications for surveillance and clinical trial design. [ABSTRACT FROM AUTHOR]

Objectives: This study examines the utility of surveillance imaging in detecting locoregional failures (LRF), distant failures (DF) and second primary tumors (SPT) in patients with human papillomavirus (HPV) associated oropharyngeal cancer (OPC) after definitive chemoradiotherapy (CRT).Methods and Materials: An institutional database identified 225 patients with biopsy proven, non- metastatic HPV+ OPC treated with definitive CRT between 2004 and 2015, whose initial post-treatment imaging was negative for disease recurrence (DR). Two groups were defined: patients with <2 scans/year Group 1 and patients with ≥2 scans/year Group 2. The Mann-Whitney test or Chi-square was used to determine differences in baseline characteristics between groups. Fine & Gray regression was used to detect an association between imaging frequency, DR and diagnosis of SPT.Results: Median follow up was 40.8 months. 30% of patients had ≥T3 disease and 90% had ≥ N2 disease (AJCC 7th edition). Twenty one failures (9.3%) were observed, 7 LRF and 15 DF. Six LRF occurred within 24 months and 14 DF occurred within 36 months of treatment completion. Regression analysis showed Group 2 had increased risk of DR compared to Group1 (HR 10.3; p = 0.002) albeit with more advanced disease at baseline. Five SPT were found (2 lung, 2 esophagus, and 1 oropharynx) between 4.5 and 159 months post-CRT.Conclusion: Surveillance imaging seems most useful in the first 2-3 years post treatment, and is particularly important in detecting DF. Surveillance scans for SPT has a low yield, but should be considered for those meeting lung cancer screening guidelines. [ABSTRACT FROM AUTHOR]