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).

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).

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).

Salivary duct carcinoma: Treatment, outcomes, and patterns of failure.

BACKGROUND: Salivary duct carcinoma is rare, with distinct morphology and behavior. We reviewed our institutional experience with salivary duct carcinoma, aiming to characterize clinical behavior and treatment outcomes. METHODS: All salivary duct carcinomas treated curatively between 1999 and 2010 were reviewed. Overall survival (OS), locoregional control, distant control, and patterns of failure were analyzed. Multivariate analysis identified predictors of OS. RESULTS: Fifty-four patients with salivary duct carcinoma (parotid gland = 49; submandibular gland = 5) were included in the analysis. Fifty-three patients underwent primary surgery, and 48 (89%) received postoperative radiotherapy (RT; median dose = 60 Gy). Median follow-up was 5.7 years. The 5-year OS, locoregional control, and distant control were 43%, 70%, and 48%, respectively. Nine local (6 involving facial nerve), 10 regional, and 28 distant failures were identified. Multiple pathologic involved lymph nodes (pN2b/N2c) predicted reduced OS (hazard ratio [HR] = 3.6; p = .02). CONCLUSION: Distant recurrence is common. Presence of pN2b/N2c disease is associated with reduced OS. Local recurrence frequently involves the facial nerves. © 2015 Wiley Periodicals, Inc. Head Neck 38: E820-E826, 2016.

Current management of anal canal cancer.

Combined-modality therapy consisting of radiation therapy and 5-fluorouracil plus mitomycin remains the standard treatment for localized anal canal cancer, permitting preservation of organ function and achieving high response and survival rates. Current trials are evaluating the ability to deliver higher doses of radiation therapy over shorter intervals. Currently, the most common indication for radical surgery is failure of chemoradiation. Metastatic disease is less responsive to chemoradiation treatment. Neoadjuvant and adjuvant strategies are being evaluated, and additional drugs including capecitabine, irinotecan, and oxaliplatin are being assessed in treatment of localized and advanced disease.

Outcomes of intensity-modulated radiotherapy versus conventional radiotherapy for hypopharyngeal cancer.

BACKGROUND: The purpose of this study was to discuss if the adoption of intensity-modulated radiotherapy (IMRT) for hypopharyngeal squamous cell carcinoma (SCC) has improved the outcome. METHODS: We compared 3-dimensional (3D) radiotherapy (RT) and IMRT in all patients with hypopharyngeal SCC treated with curative intent RT or chemoradiation therapy (CRT) from January 1, 2000, to February 28, 2010. Locoregional control, overall survival (OS), distant relapse rate, larynx preservation rate, and enteral feeding tube duration were analyzed. RESULTS: Of 181 consecutive patients, 90 received 3D-RT and 91 received IMRT. At 3 years, the IMRT group had higher locoregional control compared with the 3D-RT group (75% vs 58%; p = .003), but similar OS (50% vs 52%; p = .99), distant relapse rate (23% vs 20%; p = .79), and larynx-preservation rate (90% vs 86%; p = .16). The 2-year enteral feeding tube dependency rate was similar in both groups (19% vs 18%; p = .12). CONCLUSION: Patients with hypopharyngeal SCC treated with IMRT showed a higher locoregional control compared with 3D-RT. However, distant-relapse rate and OS remain comparable between treatment techniques.

Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas.

PURPOSE: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. METHODS AND MATERIALS: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D(prolif) of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. RESULTS: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. CONCLUSIONS: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials.

Results of radiotherapy for primary subglottic squamous cell carcinoma.

PURPOSE: To retrospectively evaluate the outcome after radical radiotherapy (RT) and surgical salvage and assess the risk of late toxicity for patients with primary subglottic squamous cell carcinoma treated at our center. METHODS AND MATERIALS: Between 1971 and 1996, 43 patients with primary squamous cell carcinoma of the subglottis (35 men, 8 women) were treated with radical RT. All received megavoltage irradiation, most commonly to a dose of 50-52 Gy in 20 fractions during 4 weeks (39 patients). The median follow-up was 4.2 years. RESULTS: Local control was achieved with RT alone in 24 (56%) of the 43 patients: 7 of 11 with T1, 8 of 12 with T2, 4 of 8 with T3, and 5 of 12 with T4. The 5-year actuarial local relapse-free rate was 52%. Subsequent local control was achieved in 11 of the 13 patients with failed RT and attempted surgical salvage, for an ultimate local control rate of 81.4% (35 of 43). The 5-year overall and cause-specific actuarial survival rate was 50.3% and 66.9%, respectively. No patients developed Grade 3 or 4 late radiation morbidity. CONCLUSION: These data support the use of primary RT in the treatment of patients with primary squamous cell carcinoma of the subglottis as an appropriate treatment approach providing an option for laryngeal conservation.

Tolerability of the Intergroup 0099 (INT 0099) regimen in locally advanced nasopharyngeal cancer with a focus on patients' nutritional status.

PURPOSE: The Intergroup 0099 trial (INT 0099) for locally advanced nasopharyngeal cancer (NPC) has set a standard of practice. This retrospective review documents our institutional experience with this regimen. METHODS AND MATERIALS: For all NPC patients treated between January 1998 and December 2002 with the INT 0099 regimen, compliance, toxicity, weight change, and feeding tube use were recorded. Patients were grouped by therapy completion status and by feeding tube status. RESULTS: Of 78 consecutive patients, 75 were evaluable. Compliance with radiotherapy was excellent. Only 43% and 61% of patients received all cycles of concurrent and adjuvant chemotherapy, respectively. Patients who successfully completed therapy had a higher average baseline weight and were more likely to have had a prophylactic feeding tube. Forty of 75 patients had a feeding tube inserted and were analyzed as two groups. Patients with prophylactic insertion (n = 23) had a more gradual drop in weight, and recovered to a greater degree at 1 year (93.6% vs. 87.2%), than those with a feeding tube inserted therapeutically during treatment (n = 17). CONCLUSIONS: The INT 0099 regimen was generally delivered with modifications to the chemotherapy component, as in the original trial. The prophylactic insertion of a feeding tube may facilitate therapy completion and weight recovery in some patients.

A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer.

PURPOSE: To test the hypothesis that the use of oral pilocarpine during and after radiotherapy (RT) for head-and-neck cancer would reduce the symptoms of post-RT xerostomia. METHODS AND MATERIALS: One hundred thirty patients were randomized in a double-blind method to receive either pilocarpine (5-mg tablets) or placebo three times daily starting on Day 1 of RT and continuing for 1 month after treatment. The eligibility criteria included a planned dose of >50 Gy as radical or postoperative RT for head-and-neck cancer, with at least 50% of both parotid glands included in the treatment fields. The primary outcome measure was the severity of xerostomia as assessed by a patient-completed linear analog scale 3 months after RT. Secondary outcome measures included quality of life during therapy (as assessed by the McMaster University Head-and-Neck Questionnaire) and severity of mucositis during RT (as assessed using Radiation Therapy Oncology Group scales). RESULTS: No difference was observed between the pilocarpine-treated patients and the placebo group in the severity of xerostomia score as assessed by linear analog scale at baseline and 1, 3, and 6 months after treatment (repeated measures analysis, p = 0.92). No difference was apparent in the severity of mucositis during RT; 56.3% of patients receiving pilocarpine had Grade III/IV mucositis compared with 50.8% treated with placebo. No difference in quality of life was noted between the treatment groups during or after RT. The questionnaire score at 3 months after RT was 5.0 (SD 1.0). in the pilocarpine group and 4.9 (SD 0.9) in the placebo group. CONCLUSION: We were unable to detect a beneficial effect of pilocarpine on RT-induced xerostomia when administered during RT for head-and-neck cancer.

Prospective evaluation of acute toxicity and quality of life after IMRT and concurrent chemotherapy for anal canal and perianal cancer.

PURPOSE: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. METHODS AND MATERIALS: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. RESULTS: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus-positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were significantly better at 12 months than at baseline. Multiple dose-volume parameters correlated moderately with diarrhea, skin, and hematologic toxicity scores. CONCLUSION: IMRT reduces acute grade 3 + hematologic and gastrointestinal toxicities compared with reports from non-IMRT series, without compromising locoregional control. The reported QOL scores most relevant to acute toxicities returned to baseline by 3 months after treatment.

A randomized controlled trial of lorazepam to reduce liver motion in patients receiving upper abdominal radiation therapy.

PURPOSE: Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion. METHODS AND MATERIALS: Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy. RESULTS: Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant. CONCLUSIONS: Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm.

Retrospective study of palliative radiotherapy in newly diagnosed head and neck carcinoma.

PURPOSE: To examine the patterns of care, outcomes, and prognostic factors for patients with head-and-neck cancer (HNC) treated with palliative radiotherapy (RT). METHODS AND MATERIALS: An institutional HNC anthology and electronic patient records were used to identify patients with previously untreated HNC of mucosal or salivary gland origin who underwent palliative RT at our institution between July 2003 and June 2008. Overall survival was determined from the start date of RT to either the date of death or the date of last follow-up for living patients. The data were censored if the subject was either lost to follow-up or had not been seen for follow-up at our institution for ≥4 months. RESULTS: We identified 148 eligible patients. The median age was 72 years (range, 19-94). Of the 148 patients, 12 had Stage II-III, 39 Stage IVA, 36 Stage IVB, and 54 Stage IVC; for 7 patients, the stage was unknown. Oropharyngeal primary cancer (40) was the most common primary site. The Eastern Cooperative Oncology Group performance status was 0 in 15, 1 in 69, 2 in 40, 3 in 19, and 4 in 5 patients. The Adult Co-morbidity Evaluation-27 scale was 0 in 33, 1 in 47, 2 in 44, and 3 in 21. The median radiation dose was 50 Gy (range, 2-70), the median fraction number was 20 (range, 1-40), and the median total treatment time (including breaks) was 29 days (range, 1-80). At analysis, 108 patients (73%) had died, 20 (13.5%) were alive, and 20 (13.5%) had been censored. The median follow-up was 4.8 months, and the median survival time was 5.2 months. Information on the treatment response was available for 103 patients (70%). On multivariate analysis, the radiation dose was an independent predictor of both overall survival (hazard ratio 0.97, 95% confidence interval 0.96-0.99, p <.01) and treatment response (odds ratio 1.05, 95% confidence interval 1.01-1.08, p <.01). CONCLUSION: For patients considered unsuitable for curative RT, the radiation dose might be an independent predictive factor for both overall survival and treatment response. Additional research is required to more effectively select those patients who might benefit from more aggressive treatment.

Lack of influence of intravenous contrast on head and neck IMRT dose distributions.

PURPOSE: Intravenous (i.v.) contrast at the time of CT-Simulation facilitates radiotherapy contouring, but may introduce a discrepancy between planned and delivered dose due to density variation in blood vessels. Here, the effect of physiologic and non-physiologic extremes of i.v. contrast densities on intensity modulated radiotherapy (IMRT) plans for patients with head and neck cancer was investigated. METHODS AND MATERIALS: This planning study was conducted using i.v. contrast CT scans of ten patients with squamous cell cancer of the head and neck treated with IMRT. The target volumes and normal tissues, including the blood vessels of the head and neck, were contoured and IMRT plans were created according to RTOG Protocol 0022. The density within the blood vessels was then virtually altered to mimic non-contrast and extreme (bone and air) densities. The dose was then recalculated using the same IMRT plan. Plans obtained with and without density overrides were then compared. RESULTS: The change in planning target volume (PTV) coverage for plans with and without i.v. contrast was minimal. The volume of the PTVs covered by the 93% and 100% isodoses changed on average by 0.57%. The minimum dose to PTVs varied by a maximum of 0.17 Gy. The maximum point dose to critical organs changed by a maximum of 0.12 Gy (brainstem). Non-physiologic extremes of density within blood vessels also resulted in minimal changes in tumor or normal tissue dosimetry. CONCLUSION: The use of i.v. contrast at time of CT-simulation does not significantly affect dose calculation in head and neck IMRT plans.

Outcomes of salvage surgery for squamous cell carcinoma of the anal canal.

BACKGROUND: For patients with anal canal cancer who fail combined modality treatment (CMT), salvage surgery (SS) offers the potential for long term survival. The literature regarding SS is limited by small patient numbers and/or heterogeneous treatment protocols. We report on a large series of patients initially treated with chemoradiation at a major referral center. METHODS: We identified 60 patients with persistent or recurrent anal cancer who had undergone SS; 20 were excluded. Overall and disease-free survival (OS, DFS) curves were constructed using the Kaplan Meier method. Univariate analysis was done using the Log-Rank test, and multivariable analysis using Cox proportional hazards. RESULTS: The 40 patients (29 women, 11 men, median age 57) underwent curative intent resection. The initial procedure was multivisceral resection (n = 24), abdominoperineal resection alone (n = 14) or local excision (n = 2). Postoperative mortality was 5%. Postoperative complications were seen in 72%. Median follow-up was 18 months overall and 36 months in survivors. Median OS was 41 months; OS and disease free survival at 5 years were 39% and 30%, respectively. Recurrence was present in 21 patients at time of analysis. Failure was locoregional in 86% (18 of 21) and distant in 48% (10 of 21). Independent predictors of poor OS were male gender, Charlson Comorbidity Score and tumor size. Independent predictors of poor disease free survival were positive margins and lymphovascular invasion. CONCLUSION: SS for anal canal cancer was associated with significant morbidity. Long-term survival was achieved in 39% of patients. Comorbidities should guide patient selection, and R0 resection should be the goal.

Molecular pathology parameters in human nasopharyngeal carcinoma.

BACKGROUND: To derive a better understanding of the biologic behavior of nasopharyngeal carcinoma (NPC), the authors evaluated a number of molecular variables to address the hypothesis that p53 dysfunction in NPC is associated with Epstein-Barr virus (EBV), increased tumor angiogenesis, lower likelihood of apoptosis, and poorer clinical outcome. MATERIALS: The biopsy samples from 87 NPC patients were obtained and sections were made to detect EBV, using in-situ hybridization; the authors used immunohistochemistry to assess p53, p21(WAF1/CIP1) expression, and microvessel density count (MVD). In situ end labelling was used to evaluate apoptosis and necrosis. Analyses were conducted on the association between each of these variables as well as clinical outcome, including survival and local control. RESULTS: There was a highly significant association between EBV-encoded RNA (EBER) positivity with p53 over-expression in that only 1 out of 32 p53 over-expressing tumors was EBER negative, as opposed to 19 out of 48 p53 negative tumors being EBER negative (P = 0.001). In addition, EBER positivity was highly associated with World Health Organization (WHO) type 3 NPC, Asian/Chinese ethnicity, a lower apoptotic index, and p21 over-expression. p53 over-expression was associated with a higher MVD count. Controlling for age and nodal status, EBER positivity was associated with both improved overall survival (P = 0.02), and disease-free survival (P = 0.04). In contrast, the presence of tumor necrosis was associated with an inferior local control (P = 0.03). CONCLUSION: p53 protein was over-expressed in approximately one third of NPC samples in the current study, and this correlated significantly with the presence of EBER. Epstein-Barr virus status was also associated with WHO type 3 NPC, Asian/Chinese ethnicity, and induction of p21. The presence of EBV appeared to predict for improved survival, the mechanism of which remains to be elucidated in this biologically complex disease.

Outcome and toxicity of postoperative short course adjuvant radiation and chemotherapy following resection of adenocarcinoma of the rectum.

A retrospective review has been performed to assess the outcome and toxicity of post-operative adjuvant therapy of 25 Gy/5 fractions/1 week following resection of stage II and III rectal cancer. Forty patients were treated between August 1992 and May 1995. The ages ranged from 42 to 79 (median 63); 32 were male (80%). At last follow up 32 were alive with 0.9 to 11.3 years of follow-up (median 6.6 years). The 5-year actuarial survival was 76% (95% CI: 62-91%). The local relapse free rate was 73% (95% CI: 58-88). Seven patients experienced grade 3 or 4 early toxicity. Three patients had grade 2 or 3 late toxicity. Although treatment was well tolerated, the local relapse rate observed was high. In view of the changes in surgical and pathological techniques in the last decade, further studies are required to determine the merits or otherwise of postoperative Short Course Adjuvant Radiation.