Impact of Definitive Chemoradiation on Quality-of-Life Changes for Patients With Anal Cancer: Long-term Results of a Prospective Study.

BACKGROUND: Maintaining and improving quality of life (QOL) are important goals of anal cancer management. This disease is generally curable, with many long-term survivors. OBJECTIVE: Long-term QOL after chemoradiation for patients with anal cancer was evaluated. DESIGN: This was a prospective cohort study. SETTINGS: This study used data from a prospective study of patients with anal cancer who were treated with chemoradiation between 2008 and 2013. PATIENTS: Patients with anal cancer who were treated with image-guided intensity-modulated radiation therapy were included. INTERVENTIONS: English-speaking patients completed European Organization for Research and Treatment of Cancer cancer-specific (C30) and site-specific (CR29) QOL questionnaires at baseline, at end of radiation, at 3 and 6 months, and then annually. MAIN OUTCOMES MEASURES: Long-term QOL was evaluated clinically (a change in score of ≥10 points was considered clinically significant) and statistically (using repeated-measurement analysis) by comparing the subscale scores at 1, 2, and 3 years with baseline scores. Subanalysis compared patients who received a radiation dose of 45 to 54 Gy versus 63 Gy. RESULTS: Ninety-six patients were included (median follow-up of 56.5 months). The symptom and functional scales showed a clinically significant decline at the end of treatment with improvement by 3 months after treatment. There was a long-term statistically significant decline in dyspnea, body image, bowel embarrassment, fecal incontinence, and hair loss, and there was long-term statistically and clinically significant worsening of impotence. Higher radiation dose (63 Gy) was not associated with significantly worse QOL. LIMITATIONS: Limitations included single-institution, single-arm study design, and lack of dose reconstruction (ie, analyses were based on prescribed, rather than delivered, dose). CONCLUSIONS: Patients with anal cancer treated with chemoradiation reported recovery of overall QOL to baseline levels. Specific symptoms remained bothersome, emphasizing the need to address and manage the chemoradiation-induced symptoms, during treatment and in the long term. See Video Abstract at http://links.lww.com/DCR/B905. IMPACTO DE LA QUIMIORRADIACIN DEFINITIVA EN CAMBIOS EN LA CALIDAD DE VIDA DE LOS PACIENTES CON CNCER ANAL RESULTADOS A LARGO PLAZO DE UN ESTUDIO PROSPECTIVE: ANTECEDENTES:Mantener y mejorar la calidad de vida son objetivos importantes del tratamiento del cáncer anal, ya que esta enfermedad generalmente es curable, con muchos sobrevivientes a largo plazo.OBJETIVO:Se evaluó la calidad de vida a largo plazo después de la quimiorradiación en pacientes con cáncer anal.DISEÑO:Este fue un estudio de cohorte prospectivo.ENTORNO CLINICO:Utilizamos datos de un estudio prospectivo en pacientes con cáncer anal tratados con quimiorradiación entre 2008-2013.PACIENTES:Los pacientes con cáncer anal fueron tratados con radioterapia de intensidad modulada guiada por imágenes.INTERVENCIONES:Los pacientes de habla inglesa completaron los cuestionarios de calidad de vida específicos de cáncer (C30) y específicos del sitio (CR29) de la Organización Europea para la Investigación y el Tratamiento del Cáncer al inicio, al final de la radiación, 3 y 6 meses, y luego anualmente.PRINCIPALES MEDIDAS DE RESULTADOS:Se evaluó a largo plazo la calidad de vida clínicamente (un cambio en la puntuación de ≥10 puntos se consideraron clínicamente significativo) y estadísticamente (usando análisis de medición repetida) comparando las subescalas de puntuación al 1, 2, y 3 años. Con puntuaciones de referencia. El subanálisis comparó pacientes que recibieron 45-54 Gy versus 63 Gy.RESULTADOS:Se incluyeron un total de 96 pacientes (mediana de seguimiento: 56,5 meses). La mayoría de las escalas funcionales y de síntomas mostraron una disminución clínicamente significativa al final del tratamiento con una mejoría a los 3 meses posteriores al tratamiento. Hubo una disminución estadísticamente significativa a largo plazo en disnea, imagen corporal, vergüenza intestinal, incontinencia fecal y pérdida de cabello; y hubo un empeoramiento a largo plazo estadística y clínicamente significativo en impotencia. La dosis de radiación más alta (63 Gy) no se asoció con una calidad de vida significativamente peor.LIMITACIONES:Institución única, diseño de estudio de un solo brazo y falta de recomposición de la dosis (es decir, los análisis se basan en la dosis prescrita, en lugar de la administrada).CONCLUSIÓNES:Los pacientes con cáncer anal tratados con quimiorradiación reportaron una recuperación de la QOL en general a los niveles de base. Síntomas específicos siguieron siendo molestos, lo que enfatiza la necesidad de resolver y tartar los síntomas inducidos por la quimiorradiación no solo durante el tratamiento, sino a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B905. (Traducción- Dr. Francisco M. Abarca-Rendon).

Anal Adenocarcinoma: A Rare Entity in Need of Multidisciplinary Management.

BACKGROUND: Anal adenocarcinoma is a rare clinical entity for which the optimal management is not defined. OBJECTIVE: This study aimed to describe the multidisciplinary management and outcomes of patients with anal adenocarcinoma. DESIGN: This is a retrospective cohort study. SETTING: This study was conducted at a quaternary cancer center. PATIENTS: Men and women with anal adenocarcinoma treated between 1995 and 2016 were selected. INTERVENTIONS: Fifty-two patients were treated with either chemoradiotherapy or trimodality therapy including radiation therapy, chemotherapy, and surgical resection. MAIN OUTCOME MEASURES: Local failure, regional failure, and distant metastasis rates were estimated using the cumulative incidence method. The Kaplan-Meier method was used to estimate progression-free survival and overall survival. The multivariable Cox proportional hazards model was used to evaluate the clinical predictors of outcome. RESULTS: There was a higher 5-year rate of local failure in patients treated with chemoradiotherapy compared with trimodality therapy (53% vs 10%; p < 0.01). The 5-year incidence of distant metastases was 29% (trimodality therapy) versus 30% (chemoradiotherapy; p = 0.9); adjuvant chemotherapy did not reduce the incidence of distant metastases (p = 0.8). Five-year overall survival was 73% (trimodality therapy) versus 49.4% (chemoradiotherapy; p = 0.1). On multivariable analysis, factors associated with worse overall survival were treatment with chemoradiotherapy, cT3-4 category disease, and node-positive disease. LIMITATIONS: This study is limited by its small sample size and retrospective nature. CONCLUSIONS: Although treatment may continue to be tailored to individual patients, better outcomes with a trimodality therapy approach were observed. See Video Abstract at http://links.lww.com/DCR/B708.ADENOCARCINOMA ANAL: UNA ENTIDAD POCO FRECUENTE EN NECESIDAD DE UN MANEJO MULTIDISCIPLINARIO. ANTECEDENTES: El adenocarcinoma anal es una entidad clínica poco frecuente por lo que aún no se define el manejo óptimo. OBJETIVO: Describir el manejo multidisciplinario y los resultados de los pacientes con adenocarcinoma anal. DISEO: Estudio de cohorte retrospectivo. ENTORNO CLINICO: Centro de cáncer cuaternario. PACIENTES: Hombres y mujeres con adenocarcinoma anal tratados entre 1995 y 2016. INTERVENCIONES: Cincuenta y dos pacientes fueron tratados con quimiorradioterapia o terapia trimodal que incluyó: radioterapia, quimioterapia y resección quirúrgica. PRINCIPALES MEDIDAS DE VALORACION: Se estimaron las tasas de falla local, falla regional y metástasis a distancia mediante el método de incidencia acumulada. Se utilizó el método de Kaplan-Meier para estimar la supervivencia libre de progresión y la supervivencia global. Los riesgos proporcionales de multivariable Cox se utilizaron para evaluar los predictores clínicos de los resultados. RESULTADOS: Hubo una mayor tasa de falla local a cinco años en pacientes tratados con quimiorradioterapia en comparación con terapia trimodal (53% vs 10%; p < 0,01). La incidencia a cinco años de metástasis a distancia fue del 29% (terapia trimodal) versus 30% (quimiorradioterapia) (p = 0,9); la quimioterapia adyuvante no redujo la incidencia de metástasis a distancia (p = 0,8). La supervivencia global a cinco años fue del 73% (terapia trimodal) versus 49,4% (quimiorradioterapia); p = 0,1. En el análisis multivariable, los factores asociados con una peor supervivencia general fueron el tratamiento con quimiorradioterapia, enfermedad de categoría cT3-4 y enfermedad con ganglios positivos. LIMITACIONES: Este estudio está limitado por su pequeño tamaño de muestra y su naturaleza retrospectiva. CONCLUSIONES: Aunque el tratamiento puede seguir adaptándose a pacientes individuales, se observaron mejores resultados con un enfoque TTM. Conslute Video Resumen en http://links.lww.com/DCR/B708. (Traducción- Dr. Francisco M. Abarca-Rendon).

A gastronomic delight?

Flagellate dermatitis (FD) exhibits a striking clinical appearance similar to whiplash marks. General dermatologists are likely to encounter this clinical appearance as a more localized presentation of phytophotodermatosis. Jellyfish stings may also cause localized linear or FD. Chemotherapeutic agents such as bleomycin, doxorubicin, docetaxel, and trastuzumab are well-recognized causes of a widespread FD and it may more rarely be seen in connective tissue disease such as dermatomyositis or Still disease. In our case, this was a presentation of shiitake mushroom dermatitis.

Effect of Multidisciplinary Cancer Conference on Treatment Plan for Patients With Primary Rectal Cancer.

BACKGROUND: Although multidisciplinary cancer conferences have been reported to lead to improved patient outcomes, few studies have reported results of these for rectal cancer. OBJECTIVE: The purpose of this work was to assess the quality of multidisciplinary cancer conferences, the effect of the conference on the initial treatment plan, compliance with the conference treatment recommendations, and clinical outcomes for rectal cancer. DESIGN: This was a prospective, longitudinal study. SETTINGS: The study was conducted at a tertiary care academic hospital. PATIENTS: Patients with primary rectal cancer were included in this study. INTERVENTION: The intervention was a rectal cancer-specific multidisciplinary cancer conference. MAIN OUTCOME MEASURES: The quality of the multidisciplinary cancer conference was assessed using the Cancer Care Ontario Multidisciplinary Cancer Conference standards score. A change in treatment plan was defined as a change from the initial treatment plan selected by the treating physician to an alternate treatment plan recommended at the conference. RESULTS: Twenty-five multidisciplinary cancer conferences were conducted over a 10-month study period. The Cancer Care Ontario Multidisciplinary Cancer Conference standards score was 7 (from a maximum score of 9). Forty-two patients with primary rectal cancer were presented, and there was a 29% (12/42) change in the initial treatment plan. A total of 42% (5/12) of these changes were attributed to reinterpretation of the MRI findings. There was 100% compliance with the conference treatment recommendations. The circumferential resection margin was positive in 5.5% (2/36). LIMITATIONS: Selection bias may have led to an overestimate of effect, and there is no control group for comparison of clinical outcomes. CONCLUSIONS: A high-quality rectal cancer-specific multidisciplinary cancer conference led to a 29% change in the treatment plan for patients with primary rectal cancer, with almost half of these changes attributed to reinterpretation of the magnetic resonance images.

Patient and staff assessment of an audiovisual education tool for head and neck radiation therapy.

The purpose of this study was to understand and compare patient and staff perceptions of a video-based preparatory education tool for head and neck radiotherapy. Patients and staff completed a questionnaire assessing their perceptions of whether the education tool was relevant, clear, complete and reassuring. Staff rated the video's accuracy and anticipated impact on future patient information needs. Demographic information was collected. Open-ended questions were used to elicit additional feedback. Quantitative responses from 50 patients and 48 staff were very positive and not significantly different between the two groups. Content analysis of the qualitative data provided insight into the information and approaches valued by patients and staff and how these differed. Staff members were more critical of the production quality and completeness of information related to procedures and treatment side effects. Patients valued seeing procedures acted out and desired more information about what these experiences would feel like and how to engage in self-care. Although staff-driven development may be an effective method of designing the content and approach of a preparatory education video, care should be taken to consider differences between patient and staff perceptions of information needs.

Can Conformity-Based Volumetric Modulated Arc Therapy Improve Dosimetry and Speed of Delivery in Radiation Therapy to Lumbosacral Spine Compared with Conventional Techniques?

PURPOSE: Volumetric modulated arc therapy (VMAT) has generally been perceived as too time and resource intensive for palliative radiation therapy mainly because of the need for extensive organs at risk contouring. Dose-limiting conformity-based objectives can be automatically generated and are commonly used to conform isodoses closely around the target volumes during inverse planning. The aim of this study was to determine if conformity-based objectives can be used to create VMAT plans for lumbosacral spine palliative radiation therapy without organs at risk contours, which will improve conformity, dose homogeneity, and speed of delivery compared with standard forward planning approaches. METHODS: A total of 25 patients were retrospectively replanned using three different planning techniques: (1) anterior-posterior parallel opposed pair (POP); (2) single isocenter anterior-posterior half-beam block junctioned to three fields, posterior and two laterals (JUNC); and (3) VMAT single arc. Treatment volume included L1-S5 vertebrae prescribed to 20 Gy in five fractions. Conformality index, homogeneity index, contour, planning, and treatment time were compared for each technique. RESULTS: Planning target volume V95 ≥95% was maintained for all 75 replans. VMAT was superior to POP and JUNC in terms of conformality (POP 2.0 vs. JUNC 1.8 vs. VMAT 1.2; P < .01) and homogeneity (POP 1.1 vs. JUNC 1.1 vs. VMAT 1.0; P < .01). Planning times for POP were the lowest (3.2 minutes). VMAT and POP had similar delivery times (1.5 minutes), which were approximately half the JUNC delivery time (3.2 minutes). CONCLUSIONS: Conformity-based VMAT was dosimetrically superior to conventional field-based planning and reduced delivery time. This reduction in normal tissue dose as well as reduced time spent on the treatment couch can potentially improve the quality of life in palliative patients receiving radiotherapy to the lumbosacral spine.

Long-term outcomes following salvage surgery for locally recurrent rectal cancer: A 15-year follow-up study.

BACKGROUND: Locally recurrent rectal cancer (LRRC) is a complex problem requiring multidisciplinary consultation and specialized surgical care. Given the paucity of published longer-term survival data, skepticism persists regarding the benefit of major extirpative surgery. We investigated ultra-long-term (~15 years) outcomes following radical resection of LRRC and sought relevant clinicopathologic prognostic variables. METHODS: A cohort of 52 consecutive patients who underwent resection of LRRC at our institution between 1997 and 2005 were followed with serial exams and imaging up to the point of death, or 30/06/2019. RESULTS: Median follow-up time was 16.5 years (9.9-18.3) for patients who were alive at last follow-up; only one patient was lost to follow-up, at 9.9 years. For the entire cohort of 52 patients, disease-specific survival (DSS) at 5, 10, and 15 years following salvage surgery was 41%, 33%, and 31%, respectively. All patients who had distant metastatic disease at the time of LRRC resection (n = 6) subsequently died of cancer, at a median of 21 months (4-46). In those without distant metastases at time of salvage surgery (n = 46), DSS at 5, 10, and 15 years was 47%, 38%, and 35%, respectively, median 60 months. Negative resection margin (R0) was independently predictive of superior outcomes. In patients with M0 disease who had R0 resection (n = 37), DSS at 5, 10 and 15 years was 58%, 47%, and 44%, respectively, median 73 months. No patient developed re-recurrence after 5.5 years. CONCLUSIONS: This study demonstrates exceptionally durable long-term cancer-free survival following salvage surgery for LRRC, indicating that cure is possible.

Durable therapeutic gain despite competing mortality in long-term follow-up of a randomized hyperfractionated radiotherapy trial for locally advanced head and neck cancer.

PURPOSE/OBJECTIVES: To examine the therapeutic ratio and mortality profile over time in a radiotherapy randomized trial in stage III-IV larynx/pharynx cancer with long-term follow-up. MATERIALS/METHODS: From 1988 to 1995, 331 cases were randomized to either hyperfractionated (HF) (58 Gy/40 fractions, twice daily) or conventional (CF) (51 Gy/20 fractions, once daily) radiotherapy. Overall survival (OS), locoregional (LRC), distant control (DC), ≥Grade 3 late toxicity (LT), and relative mortality risk profile over time were compared between both arms. RESULTS: Median follow-up was 13.6 years. HF had a 10% improved OS at 5-years (40% vs 30%, p = 0.04), but the benefit diminished to 3% at 10-years (21% vs 18%). A trend towards higher LRC with HF remained (5-year: 49% vs 40%; 10-year: 49% vs 39%, p = 0.05). DC rates were unchanged (5-year: 87% vs 85%; 10-year: 87 vs 84%, p = 0.56). LT rates were similar (HF vs CF: 5-year: 9% vs 12%; 10-year: 11% vs 14%, p = 0.27). Multivariable analysis confirmed that HF reduced mortality risk by 31% [HR 0.69 (0.55-0.88), p < 0.01] and locoregional failure risk by 35% [HR 0.65 (0.48-0.89), p < 0.01]. Index cancer mortality (5-year: 46% vs 51%; 10-year: 49% vs 55%) was lower in the HF arm. Competing mortality (mostly smoking-related) was also numerically lower with HF at 5-years (14% vs 19%) but became similar at 10-years (30% vs 28%). CONCLUSIONS: This trial confirms that HF with augmented total dose has a durable 10% effect size on LRC with comparable LT. OS benefit is evident at 5-years (10%) but relative mortality risk profile changes in longer follow-up.

Effect of concurrent high-dose cisplatin chemotherapy and conformal radiotherapy on cervical esophageal cancer survival.

PURPOSE: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. METHODS AND MATERIALS: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m(2)) on Days 1-4 and either mitomycin C (10 mg/m(2)) or cisplatin (75 mg/m(2)) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m(2)) on Days 1, 22, and 43. RESULTS: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age < or =64 years, 34%; p = 0.10). CONCLUSION: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes.

Hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer: quality of life in a prospective phase I/II trial.

BACKGROUND AND PURPOSE: Quality of life (QOL) was measured prospectively in a dose escalation study of twice daily hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer (HNC). MATERIALS AND METHODS: Patients with squamous cell HNC (TNM stage III/IV larynx or pharynx, or hypopharynx any stage) received 40 fractions of twice daily RT at 3 dose levels: (L1) 60Gy, 1.5Gy/fraction; (L2) 62Gy, 1.55Gy/fraction; and (L3) 64Gy, 1.6Gy/fraction. QOL was measured on the FACT-H&N at baseline, 6 and 12 months. RESULTS: Mean QOL scores were: baseline 104, 6 months 108, 12 months 112. At all time points, QOL scores were lower in patients with more advanced T-category. A mixed-model analysis of determinants of QOL showed no dose effect among L1 (n=22), L2 (n=26) or L3 (n=123). QOL improved significantly with time from diagnosis, however post-treatment QOL was lower and improved more slowly in patients who had feeding tubes. CONCLUSIONS: Post-RT QOL improved from baseline by a statistically and clinically significant amount. Hyperfractionated, accelerated RT provides favorable QOL outcomes, and is a viable alternative to chemoradiation for patients with locally advanced HNC.

A dose escalation study of hyperfractionated accelerated radiation delivered with integrated neck surgery (HARDWINS) for the management of advanced head and neck cancer.

BACKGROUND AND PURPOSE: To determine toxicity and outcome of radiation dose escalation with hyperfractionated accelerated radiation delivered with neck surgery (HARDWINS) for head and neck cancer. PATIENTS AND METHODS: Patients with stage III and IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx were enrolled. Dose levels of 60, 62 and 64Gy were delivered with twice daily fractionation in 40 fractions over 4 weeks. Involved and at-risk nodal regions received microscopic dose (46.5-48Gy) with neck dissection for node positive patients 8 weeks after radiation. RESULTS: One hundred and sixty-nine patients were enrolled (60Gy n=22, 62Gy n=26, 64Gy n=121). No grade 4 acute toxicity was observed. Incidence of acute grade 3 toxicity was: skin (2%), larynx (6%), pharynx and esophagus (66%) and mucous membrane (75%). Feeding tube dependence was observed in 14% of patients receiving 64Gy. Overall survival, and relapse free rate at 5 years were 65% and 63%, respectively. Local, nodal and distant relapse free rates at 5 years were 77%, 94% and 81% (median follow-up 3.8 years). CONCLUSIONS: HARDWINS can be delivered without acute grade 4 toxicity but significant grade 3 acute toxicity. A significant proportion of the patients have prolonged swallowing dysfunction. Outcomes suggest this regimen represents an alternative to chemoradiation.

The ongoing challenge of large anal cancers: prospective long term outcomes of intensity-modulated radiation therapy with concurrent chemotherapy.

PURPOSE: Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer. METHODS: Between 2008-2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27-36 Gy for elective target, and 45-63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed. RESULTS: Overall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF (n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF (n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%]). CONCLUSIONS: Individualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study.

PURPOSE: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2)) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer.

Intraobserver and interobserver variability in GTV delineation on FDG-PET-CT images of head and neck cancers.

PURPOSE: To determine if the addition of fluorodeoxyglucose positron emission tomography (FDG-PET) data changes primary site gross tumor volumes (GTVs) in head and neck cancers. METHODS AND MATERIALS: Computed tomography (CT), contrast-enhanced CT, and FDG-PET-CT scans were obtained in 10 patients with head and neck cancers. Eight experienced observers (6 head and neck oncologists and 2 neuro-radiologists) with access to clinical and radiologic reports outlined primary site GTVs on each modality. Three cases were recontoured twice to assess intraobserver variability. The magnitudes of the GTVs were compared. Intra- and interobserver variability was assessed by a two-way repeated measures analysis of variance. Inter- and intraobserver reliability were calculated. RESULTS: There were no significant differences in the GTVs across the image modalities when compared as ensemble averages; the Wilcoxon matched-pairs signed-rank test showed that CT volumes were larger than PET-CT. Observers demonstrated the greatest consistency and were most interchangeable on contrast-enhanced CT; they performed less reliably on PET-CT. CONCLUSIONS: The addition of PET-CT to primary site GTV delineation of head and neck cancers does not change the volume of the GTV defined by this group of expert observers in this patient sample. An FDG-PET may demonstrate differences in neck node delineation and in other disease sites.

Five year results of a randomized trial comparing hyperfractionated to conventional radiotherapy over four weeks in locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: Fractionation strategies delivered over 4 weeks are of clinical and radiobiological interest because treatment is completed before radiotherapy (RT) induced clonogen proliferation commences in earnest approximately 3 to 4 weeks into a course of RT. We wished to test the clinical hypothesis that an increased total dose delivered over 4 weeks with smaller than standard doses per fraction in locally advanced squamous cell carcinoma (SCC) may result in relative protection of late responding tissues and an increased tumor control compared to a conventional daily course in the same overall time. MATERIALS AND METHODS: Between 1988 and 1995 a randomized controlled trial employing RT alone was undertaken at the Princess Margaret Hospital that included 331 eligible patients with T3 or T4 N0 or any N-positive oropharynx, hypopharynx, or larynx primary SCC. RT was randomly assigned to one of two 4 week schedules, either 51 Gy in 20 equal daily fractions, termed conventional fractionation (CF), or 58 Gy in 40 equal fractions given twice per day as a hyperfractionated (HF) experimental arm. RESULTS: The 5-year local relapse rate was reduced in the HF (41%) compared to the CF arm (49%). This difference was marginally not significant (p=0.082) when the effect was not adjusted. When the effect of the treatment was adjusted by Cox model for clinical factors that included N-category, ECOG performance status, site of disease, T-category, age, hemoglobin, and gender the HF achieved a significant effect (p=0.02). Survival (40% vs. 30%) was also improved with HF compared to CF arm. This difference was only marginally not significant (p=0.069) but again achieved statistical significance when the model was adjusted for clinical factors (p=0.01). Similar results were observed for disease free survival. Although reversible acute toxicity was increased with HF, the overall 5-year rate of grade 3 and 4 late toxicity for the CF was 10.5% compared to 7.7% in the higher dose HF arm. CONCLUSIONS: HF delivered in 4 weeks permits enhanced RT doses achieving improved tumor control, without increased late toxicity, compared to daily fractionated radiotherapy in the same overall time.

Investigation of volumetric apparent diffusion coefficient histogram analysis for assessing complete response and clinical outcomes following pre-operative chemoradiation treatment for rectal carcinoma.

PURPOSE: To investigate the relationship of pre-treatment volumetric apparent diffusion coefficient (ADC) histogram parameters with post-operative histopathologic treatment response and clinical outcomes following pre-operative chemoradiation treatment (CRT) in rectal cancer. MATERIALS AND METHODS: In a Health Insurance Portability and Accountability Act compliant retrospective study, 78 rectal cancer patients treated with pre-operative CRT and rectal MRI were included. MR imaging analysis was performed using OncoTREAT (software tool). Multiple volumetric ADC histogram parameters (voxel distribution across ADC ranges, kurtosis, and skewness) were assessed. Correlation was made to post-operative pathological complete response, clinical, or radiological evidence of disease progression using the Mann-Whitney test. RESULTS: Post CRT, 8 patients showed pathologic complete response and 13 patients showed distant disease progression. Pre-treatment mean ADC was 1.2 × 10-3 mm2/s (range 0.3-1.99 × 10-3 mm2/s). Mean kurtosis measured was 0.56 (range -1 to 6; SD 1.36). Mean skewness was 0.3 (range -1 to 2; SD 0.69). Skewness had significant correlation (p value = 0.006) with disease progression. The mean rectal tumor volume was 24cc (range 1cc-134cc). Pre-treatment MRI tumor volume showed significant correlation (p value = 0.013) with pathologic complete response. Mean ADC and percentage voxels distribution against ADC ranges had no significant correlation with treatment response or disease outcomes. CONCLUSION: Volumetric ADC histogram analysis of pre-CRT rectal cancer MRI appears promising for prediction of post-CRT complete response and disease progression.

Bridging Innovation and Outreach to Overcome Global Gaps in Radiation Oncology Through Information and Communication Tools, Trainee Advancement, Engaging Industry, Attention to Ethical Challenges, and Political Advocacy.

An evolving paradigm in global outreach in radiation oncology has been the implementation of a more region-specific, needs-based approach to help close the gap in radiation services to low- and middle-income countries through the use of innovative tools in information and communication technology. This report highlights 4 information and communication technology tools in action today: (1) the NCCN Framework for Resource Stratification of NCCN guidelines, (2) ASTRO e-Contouring, (3) i.treatsafely.org, and (4) ChartRounds.com. We also render special consideration to matters related to global outreach that we believe require distinct attention to help us meet the goals established by the 2011 United Nations׳ Declaration on noncommunicable diseases: (1) trainee advancement toward careers in global health, (2) ethical challenges of international outreach, (3) critical importance of political advocacy, and (4) collaboration with Industry.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma.

PURPOSE: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). METHODS AND MATERIALS: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. RESULTS: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). CONCLUSIONS: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases.

BACKGROUND: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). METHODS AND MATERIALS: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. RESULTS: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. CONCLUSION: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival.

PURPOSE: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m2/day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. RESULTS: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). CONCLUSIONS: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy.