Abdelkarim Said Allal

Concomitant Cisplatin Significantly Improves Locoregional Control in Advanced Head and Neck Cancers Treated With Hyperfractionated Radiotherapy

PURPOSE To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Standardized Uptake Value of 2-[18F] Fluoro-2-Deoxy-d-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy

PURPOSE In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. PATIENTS AND METHODS We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. RESULTS In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P =.01) and DFS (42% v 79%, P =.005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. CONCLUSION FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.

HIV-Specific Differences in Outcome of Squamous Cell Carcinoma of the Anal Canal: A Multicentric Cohort Study of HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy

PURPOSE To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART). PATIENTS AND METHODS A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated. RESULTS HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04). CONCLUSION Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.

Sphincter-sparing surgery after preoperative radiotherapy for low rectal cancers: feasibility, oncologic results and quality of life outcomes

The present study assesses the choice of surgical procedure, oncologic results and quality of life (QOL) outcomes in a retrospective cohort of 53 patients with low-lying rectal cancers (within 6 cm of the anal verge) treated surgically following preoperative radiotherapy (RT, median dose 45 Gy) with or without concomitant 5-fluorouracil. QOL was assessed in 23 patients by using two questionnaires developed by the QOL Study Group of the European Organization for Research and Treatment of Cancer: EORTC QLQ-C30 and EORTC QLQ-CR38. After a median interval of 29 days from completion of RT, abdominoperineal resection (APR) was performed in 29 patients (55%), low anterior resection in 23 patients (20 with coloanal anastomosis) and transrectal excision in one patient. The 3-year actuarial overall survival and locoregional control rates were 71.4% and 77.5% respectively, with no differences observed between patients operated by APR or restorative procedures. For all scales of EORTC QLQ-C30 and EORTC QLQ-CR38, no significant differences in median scores were observed between the two surgical groups. Although patients having had APR tended to report a lower body image score (P = 0.12) and more sexual dysfunction in male patients, all APR patients tended to report better physical function, future perspective and global QOL. In conclusion, sphincter-sparing surgery after preoperative RT seems to be feasible, in routine practice, in a significant proportion of low rectal cancers without compromising the oncologic results. However, prospective studies are mandatory to confirm this finding and to clarify the putative QOL advantages of sphincter-conserving approaches.

Imaging of the larynx and hypopharynx

The purpose of this article is to review currently used imaging protocols for the evaluation of pathologic conditions of the larynx and hypopharynx, to describe key anatomic structures in the larynx and hypopharynx that are relevant to tumor spread and to discuss the clinical role of Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and PET CT in the pretherapeutic workup and posttherapeutic follow-up of patients with squamous cell carcinoma of this region. A detailed discussion of the characteristic neoplastic submucosal invasion patterns, including extension to the preepiglottic space, paraglottic space and laryngeal cartilages and the implications of imaging for tumor staging and treatment planning is provided. The present article also reviews less common tumors of this region, such as chondrosarcoma, lymphoma, minor salivary gland tumors and lipoma. As the majority of non-neoplastic conditions do not require imaging the role of CT and MRI is discussed in some particular situations, such as to delineate cysts and laryngoceles, abscess formation in inflammatory conditions, to evaluate laryngeal and hypopharyngeal involvement in granulomatous and autoimmune diseases, and to evaluate the extent of laryngeal fractures due to severe blunt trauma.

The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy

PURPOSE To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. METHODS The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). RESULTS Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age < or = 65, male gender, and gap > 37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p = 0.01), and gap (p = 0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. CONCLUSION In anal cancers, split-course RT with > 50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients.

Assessment of long-term quality of life in patients with anal carcinomas treated by radiotherapy with or without chemotherapy.

SummaryThis study was conducted to assess long-term Quality of Life (QOL) in patients treated by radiotherapy with or without chemotherapy for anal carcinomas. Patients with a maximum age of 80 years, and who were alive at least 3 years following completion of treatment with a functioning anal sphincter and without active disease, were selected for this study. Of 52 such patients identified, 41 (79%) were evaluable. There were 35 females and six males with a median age of 71 years (55–80). The median follow-up interval was 116 months (range 37–218). QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer: one for cancer-specific QOL (EORTC QLQ-C30) and one for site-specific QOL (EORTC QLQ-CR38). For the function scales a higher score represents a higher level of functioning (100 being the best score), whereas for the symptom scales a higher score indicates a higher level of symptomatology/problems (0 being the best score). For the QLQ-C30, the functional scale scores ranged from 71 (global quality of life) to 85 (role function) and the symptom scale scores from 6 (nausea-vomiting) to 28 (diarrhoea). For the QLQ-CR38 module the functional scale scores ranged from 13 (sexual functioning) to 74 (body image) and for the symptom scale scores from 5 (weight loss) to 66 (sexual dysfunction in males). None of the functional and symptom scale scores seemed to be better in patients with longer follow-up. In patients treated with sphincter conservation for anal carcinomas, long-term QOL as measured by the EORTC QLQ-C30 and QLQ-CR38 appears to be acceptable, with the exception of diarrhoea and perhaps sexual function. Moreover, the subset of patients who presented with severe complications and/or anal dysfunction showed poorer scores in most scales.

Quality of life in patients with oropharynx carcinomas: assessment after accelerated radiotherapy with or without chemotherapy versus radical surgery and postoperative radiotherapy

In oropharyngeal carcinomas, it is assumed that the effectiveness of the different treatment approaches is roughly equivalent, whereas the functional outcome after radical radiotherapy (RT) is superior to that associated with primary surgery. The aim of this study is to assess quality of life (QoL) outcomes of patients after two treatment strategies: radical surgery with postoperative RT and accelerated concomitant boost RT with or without chemotherapy.

CHEMORADIOTHERAPY VERSUS RADIOTHERAPY ALONE FOR ANAL CANCER: A RETROSPECTIVE COMPARISON

PURPOSE To evaluate the effect of adding one cycle of concomitant chemotherapy to curative radiotherapy on tumor control and toxicity in the treatment of anal cancer. METHODS AND MATERIALS One hundred twenty-five patients completed curative sphincter-conserving treatment, 57 with radiotherapy alone and 68 with concomitant chemo-radiotherapy. Compared with chemoradiotherapy patients, radiotherapy patients were older (median age 71 vs 63) and had less advanced tumors (T3-4 26% vs 51%). Radiotherapy patients were usually treated with a direct perineal cobalt field (mean dose 31 Gy at 5 cm/10 fractions/3 weeks), complemented in most cases by a sacral are field, followed (mean split 54 days) by Iridium-192 implantation (mean dose 23 Gy, Paris system). The large majority of chemoradiotherapy patients received antero-posterior opposed 10 MV photon fields, including pelvic and inguinal nodes (mean dose 38 Gy/19 fractions/4 weeks), followed (mean split 42 days) by implant boost (mean dose 18 Gy). In addition, chemo-radiotherapy patients received starting on day 1 an IV bolus of Mitomycin-C, 0.4 mg/kg (maximum 20 mg) and a 5-day continuous infusion of 5-fluorouracil 600-800 mg/m2/day. Median follow-up was 65 months for radiotherapy and 48 months for chemo-radiotherapy patients. RESULTS For all 125 patients at 5 years, overall survival was 65.5%, definitive local control 83% and local control with sphincter preservation 68%. Overall and stage for stage, there was no difference in overall, progression-free or cancer-specific survival, nor in local control, local-regional control, or sphincter preservation rates between patients treated with chemoradiotherapy vs. radiotherapy alone. There was no significant difference between the two groups regarding acute or late toxicity. CONCLUSION This retrospective analysis does not confirm the efficacy of one course of simultaneous Mitomycin-C and 5-fluorouracil, at least in association with full-dose radiotherapy incorporating Iridium-192 boost.

Salvage surgery after radical accelerated radiotherapy with concomitant boost technique for head and neck carcinomas.

Definitive radiotherapy (RT) for head and neck cancer is increasingly used to preserve organ function, whereas surgery is reserved for treatment failure. However, data are sparse regarding the feasibility of salvage surgery, particularly for unselected patients after accelerated RT.