Squamous cell carcinoma of the larynx with subglottic extension: is larynx preservation possible?

PURPOSE: Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients. PATIENTS AND METHODS: Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76%. Patients received surgery (62%), radiotherapy (RT) (18%), or induction chemotherapy (CT) (20%) as front-line therapy. RESULTS: The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59% (95% CI 51-68), 83% (95% CI 77-89), and 88% (95% CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95% CI 1.2-3.6; HR1.9, 95% CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95% CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55% (95% CI 43-68), with 36% in T3 patients. The 5-year larynx preservation rate was 81% (95% CI 65-96) and 35% (95% CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively. CONCLUSION: Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT).

Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients.

PURPOSE: To review our experience using full-dose external reirradiation given with a curative intent for patients with unresectable head and neck carcinoma (HNC). PATIENTS AND METHODS: Between January 1980 and December 1996, 169 patients who presented with unresectable nonmetastatic HNC in a previously irradiated area were included in this series. The median time between the first and the second irradiation was 33 months. Reirradiation protocols were as follows: radiotherapy alone (65 Gy over 6.5 weeks at 2 Gy/d), 27 patients; Vokes protocol, ie, five to six cycles of radiotherapy (median total dose, 60 Gy; 2 Gy/d) with simultaneous fluorouracil (5-FU) and hydroxyurea, 106 patients; and bifractionated radiotherapy (median total dose, 60 Gy; 2 x 1.5 Gy/d) with concomitant mitomycin, 5-FU, and cisplatin, 36 patients. The median cumulative dose of the two irradiations was 120 Gy. Eighty-five percent of the tumors were squamous cell carcinoma, 14% undifferentiated carcinoma of nasopharyngeal type, and 1% adenocarcinoma. Forty-four percent were local recurrences, 23% nodal recurrences, 14% both local and nodal, and 19% second primary tumors. RESULTS: Mucositis grade 3 (World Health Organization [WHO]) was found in 32% and grade 4 in 14% of cases. Four patients presented with neutropenia or thrombocytopenia (grade 3 or 4 WHO). Late toxicities (> 6 months) were as follows: cervical fibrosis (grade 2 to 3 Radiation Therapy Oncology Group [RTOG]), 41%; mucosal necrosis, 21%; osteoradionecrosis, 8%; and trismus, 30%. Five patients died of carotid hemorrhage, apparently in complete remission. Six months after the onset of reirradiation, 37% of patients were in complete response. Patterns of failure were local only (53%), nodal only (20%), metastatic only (7%), and multiple (20%). Median follow-up time was 70 months. Overall survival rate (Kaplan-Meier) was 21% (95% confidence interval [CI], 15% to 29%) at 2 years and 9% (95% CI, 5% to 16%) at 5 years. Median survival time was 10 months for the entire population. Thirteen patients, of whom 12 were treated with the Vokes protocol, were long-term disease-free survivors. In a multivariate analysis, the volume of the second irradiation was the only factor significantly associated with the risk of death: relative risk=1.8 (95% CI, 1.13 to 5.7) (P=.01). CONCLUSION: Full-dose reirradiation combined with chemotherapy was feasible in patients with inoperable HNC. The incidence and severity of late toxicity was markedly increased in comparison to that observed after the first irradiation. Median survival was better than that generally obtained using palliative chemotherapy alone. A small proportion of patients were long-term disease-free survivors.

Radiotherapy in head and neck cancer in the elderly: a challenge.

Elderly patients represent the most rapidly growing subgroup of the patient population in France and in the majority of industrialized countries. The effect of age in terms of the prognosis and response to treatment remains unclear. The management strategy (curative versus palliative) for head and neck cancer in the elderly has given vent to divergent opinions and controversies in several respects (the type and quality of treatment, quality of life and economic consequences). This review only focuses on the radiotherapy schedule and head and neck cancers. We compare aged patients with head and neck cancer to younger patients in terms of clinical features, tumor biology, type of treatment, side effects and response. We conclude that if the patient is in a good general condition following a complete evaluation of the cancer, physicians should propose curative treatment with radiotherapy because retrospective trials demonstrate that response in older patients when treated aggressively is comparable to that of younger patients. However, specific trials concerning aged patients with head and neck cancer, quality of life and radiotherapy are warranted.

Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma.

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.

Results of a phase II trial of epirubicin and cisplatin (EP) before and after irradiation and 5-fluorouracil in locally advanced pancreatic cancer: an EORTC GITCCG study.

The objective of the present study was to define the role of chemotherapy, in the form of the EP regimen, consisting of epirubicin (E) and cisplatin (P) in addition to irradiation in combination with 5-fluorouracil (5-FU) for treatment of pancreatic cancer. 53 eligible patients with histologically or cytologically proven locally advanced pancreatic cancer were treated with three cycles of E 60 mg/m2 (if this dose was well tolerated then the dose of E was increased by 10 mg/m2 in the next cycle; 80 mg/m2 was the maximum dose for the following cycles) and P 100 mg/m2 once every 3 weeks, followed after 4 weeks by a split course of irradiation of 40 Gy with 5-FU 500 mg/m2 on each of the first 3 days of each 20 Gy treatment segment. This was followed by another three cycles of EP in patients who achieved stable disease (SD) or a better response after the first three cycles. The treatment given with standard anti-emetics was moderately tolerated. The chemotherapy related toxicity consisted mainly of myelosuppression and the chemoradiotherapy related toxicity of gastrointestinal side-effects. However, due to the long duration of treatment which made the whole treatment difficult to endure, only 18/53 (34%) actually completed the full treatment regimen. Responses were evaluated after the first three cycles and 4 weeks after the completion of the treatment by serial CT-scans using standard criteria. The results in 53 evaluable patients after the first three cycles of EP were as follows: 1 patient achieved a clinical complete response (CR), 7 a partial response (PR) (CR + PR: 15%; 95% confidence interval (CI): 11-33%), 36 patients (68%) had stable disease (SD) and 6 patients progressive disease (PD). There was 1 early PD, 1 toxic death and 1 patient could not be evaluated. The response at the end of the treatment was 3 CR, 11 PR (CR + PR: 14/53 (26%); 95% CI: 15-40%), 30 SD and 6 PD. The median time to progression was 8.9 months and the median duration of response 13.1 months. The median survival of all treated patients was 10.8 months (range 7 days to 41.5 months), of responders 15.1 months and, of the patients with SD 10.3 months. These results are comparable to other combined modality regimens reported in the literature for locally advanced disease. The addition of the systemic treatment with E and P offers no additional advantage to combined modality treatment alone.

Accelerated radiation therapy in the treatment of very advanced and inoperable head and neck cancers.

PURPOSE: A Phase II trial testing a continuous and accelerated regimen of radiotherapy in very advanced head and neck cancers. METHODS AND MATERIALS: From 1988 to 1990, 47 patients with very advanced and inoperable tumors (38/47 T4) of the oral cavity and the oropharynx were submitted to a continuous and accelerated regimen of hyperfractionated radiation therapy: three daily fractions of 0.9 Gy were delivered 5 days-a-week, up to the 70 Gy total dose, reducing the overall treatment time to 5.5 weeks. RESULTS: Immediate tolerance was good: only 56% of the patients experienced a Grade 3 mucositis, and the mean weight loss was 2 kg. The 2-year survival rate was 24.6%. The 2-year local control rate was 42.6%, which compares favorably with the 20% local control rate obtained in a historical control group of patients treated with another hyperfractionated regimen between 1978 and 1986. Mid- and long-term tolerance were excellent, no late complication or sequellae were observed which was also quite different from our previous experience. CONCLUSION: These results suggest an improvement of the local control and the therapeutic ratio with acceleration of radiotherapy in head and neck cancers.

Exclusive radiation therapy: the treatment of early tonsillar tumors.

One hundred and ninety-three T1 or T2 tumors of the tonsillar region have been treated by exclusive external irradiation between 1970 and 1982. Seventy-five percent of these tumors were classified as T2. There was no relationship between T and N stages. The nodal involvement was essentially linked to the macroscopic appearance of the tumor (superficial or nodular) and to the histology. The 5-year survival rate of the whole population was 58%. N stage and macroscopic appearance only influenced the survival. The local control was 88% for T1, 79% for T2. The main prognostic factors for local control were the histological type, with a 93% local control rate for poorly differentiated tumors versus 73% for well differentiated ones, and the macroscopic appearance, with a 83% local control rate for nodular tumors versus 75% for superficial ones. Superficial tumors spreading forward the anterior pilar have a higher local failure rate. All the patients' charts have been reviewed, and we observed a high percentage of marginal recurrences. The technique of irradiation, above all in case of a superficial tumor, must take into account the possibility of "geographic miss" and keep large safety margins.

External irradiation plus curietherapy boost in 108 base of tongue carcinomas.

From 1960 to 1983, 108 patients underwent an association cobaltherapy plus curietherapy boost for a base of tongue carcinoma. This group included 18 T1 tumors, 39 T2, and 51 T3. Cobaltherapy was delivered to a dose of 45 Gy/4.5 weeks to the primary site and the neck. It was completed by an electron boost or a nodal surgery in case of initial nodal disease. Two techniques of Curietherapy were used: plastic tubes and guide-gutters. As most of these implants have been done before 1975, all the doses have been recalculated on the 85% isodose according to the Paris system. They varied from 22 to 88 Gy. The tolerance of the implantation was excellent. Five-year survival of the whole group is 26%. The local control rate is 85% for T1 tumors, 50% for T2, and 69% for T3. Despite the importance of cumulated doses, a few necrosis were observed. Considering the poor outlook of this cancer, its treatment by exclusive radiotherapy requires very high doses which can only be delivered without major sequellae or complication by a combination of cobaltherapy and curietherapy boost.

Radiation therapy for head and neck cancers in the elderly.

Three hundred and thirty-one patients, aged more than 70 years, were treated for an upper aerodigestive tract carcinoma from 1978 to 1983. Larynx accounted for 28% of the primary sites, oropharynx for 27%, and the oral cavity for 16%. One-third of these patients had a contraindication to anesthesia. The treatment was consistent with our protocols in only half of the cases. Fifty-nine patients underwent a radiosurgical combination; 249 underwent an exclusive irradiation with a curative intent. Fifty-four patients underwent a palliative irradiation, which lead up to a "curative dose" in half of the cases. The immediate and long-term tolerance of the irradiation was good. The local control was 71% for patients treated with a curative intent and 19% for the palliatively irradiated patients. Five-year survival of the population was 33%. No significant relationship between age, general status, and the carcinologic outcome could be observed.

Interstitial radiation therapy for squamous cell carcinoma of the tonsillar region: the Creteil experience (1971-1981).

From July 1971 to December 1981, 33 selected patients with T1, T2 tumors of the tonsillar region were treated according to the following protocol: 1. Telecobalt therapy to the primary site and to neck nodes to a dose of 45 Gy. 2. Brachytherapy to the primary site to a dose of 30 Gy using iridium 192. 3. Boost dose to involved neck nodes with electrons, or radical neck dissection, whether N1, N2, or N3. The actuarial disease-free survival was 76% when all patient groups were included and 80% for the N0 patients. The local control rate was 100%. Disease control in the neck was 94% overall and 100% for the N0 group. These results favor the use of this protocol for superficial, minimally infiltrating tumors less than 4 cm in diameter, without obvious extension to the base of the tongue or retromolar trigone.

Very accelerated radiation therapy: preliminary results in locally unresectable head and neck carcinomas.

PURPOSE: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days. RESULTS: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco-regional control rate was 59% (95% confidence interval, 45-73%). CONCLUSIONS: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer.

A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma.

PURPOSE: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m(2), amifostine (Ethyol, U.S. Bioscience) 15-30 min prior to each radiation session. RESULTS: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of "at least Grade 3" mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months. CONCLUSION: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.

Abdominoperineal resection combined with pre- and postoperative radiation therapy in the treatment of low-lying rectal carcinoma.

PURPOSE: A series of patients with rectal carcinoma irradiated by a sandwich technique combined with surgery is retrospectively analyzed. METHODS AND MATERIALS: From 1978 to 1991, 155 patients with low or mid rectal carcinoma received abdominoperineal resection combined with a preoperative irradiation regimen of 35 Gy delivered in 14 fractions of 2.5 Gy each over a period of 3.5 weeks. The dose was increased to 45 Gy in the case of tumor fixation. According to histopathological findings, this irradiation was complemented in 87 cases by a postoperative dose of 25 Gy delivered in 10 fractions, for a total dose of 60 Gy delivered in the posterior pelvis. RESULTS: Five-year survival was 66.8% for the entire population. The 5-year actuarial local control rate was 77.6%. Carcinologic results and toxicity were analyzed according to the pathological findings and the modalities of radiation therapy. CONCLUSIONS: The postoperative boost after a preoperative moderate dose of irradiation seems to have no utility. Thus, this sandwich technique is not recommended.

Interstitial radiation therapy for carcinoma of the penis using iridium 192 wires: the Henri Mondor experience (1970-1979).

From 1970 to 1979, a group of 50 patients was treated for squamous cell carcinoma of the penis by interstitial irradiation using an afterloading technique and iridium 192 wires. The group included 9 patients with T1 tumors, 27 with T2 tumors, and 14 with T3 tumors. Forty-five patients presented with no metastatic inguinal nodes (N0), 3 patients with N1 nodes, and 2 patients had N3 nodes. After treatment, 11 patients (1 T1, 6 T2 and 4T3) developed local recurrences; 10 of these 11 patients underwent penile amputation which controlled the tumor in 7 of the patients. One patient refused amputation. Three patients developed post-therapeutic necrosis which necessitated partial amputation in 2 cases. Eight patients developed post-therapeutic urethral stenosis, which required surgical treatment in three of the cases. Overall, at their last follow-up examinations, 74% of the patients were free of disease with conservation of penile morphology and function. Most patients without metastatic nodes (37/45) at diagnosis did not receive prophylatic treatment of the groin. Two of these patients developed delayed metastatic nodes; one was successfully salvaged. All 5 patients presenting with metastatic nodes at diagnosis died, four with uncontrolled regional disease. Twenty-one percent of the patients died of their disease. We advocate interstitial irradiation using iridium 192 wires for the treatment of non-infiltrating or moderately infiltrating squamous cell carcinoma of the penis in which the largest dimension does not exceed 4 cm. Pre-implant circumcision and regular long-term follow-up are necessary. More extensive tumors are better managed surgically. When regular follow-up can be assured, it is reasonable to forgo prophylactic treatment of the inguinal nodes in patients presenting without groin metastasis.

Radiation therapy in the treatment of early glottic carcinoma: the experience of Villejuif.

A retrospective analysis of 197 early glottic carcinoma treated with small field irradiation to a dose of 65 Gy is presented. The 5-year survival rate was 77.3%. Thirty-eight local failures have been observed, and the 5-year local control rate was 85.7%. Suspicion of extra glottic extension was the main prognostic factor. Final local control rate, taking into account the salvage treatment, was 90% at 5 years. Excellent functional results were observed.

Changes in the oxygenation of head and neck tumors during carbogen breathing.

The oxygenation of head and neck tumors and changes during carbogen breathing were assessed in 20 patients. The median oxygen tension (pO2) for each patient was lower in tumors before breathing carbogen than in normal tissues. The median pooled pO2 of all the tumors was 20 mmHg; for normal tissue it was 60 mmHg. Low values (below 10 mmHg) were found in 4 patients for the normal tissue and in 18 patients for tumors. During carbogen breathing, the median (61 mmHg) pO2 readings for all tumors was higher than that recorded before carbogen breathing. The frequency of low (< 10 mmHg) pO2 values decreased with carbogen breathing in 11 patients; only 4 patients still exhibited very low values (< 2 mmHg). Maximal effect was obtained within 1-6 min of gas exposure. The pO2 stayed high under carbogen breathing in 15 out of 16 patients. Return to pre-carbogen levels of oxygenation occurred in 1 min after the end of gas exposure. These data suggest that carbogen breathing increases tumor oxygenation as assessed by polarography. The breathing time appears to be important for therapeutical use and should to be taken into consideration.

Limited small cell lung cancer treated by combined radiotherapy and chemotherapy: evaluation of a grading system of lung fibrosis.

A grading system of radiological fibrosis was defined and applied by four observers for the reading of 218 posterior-anterior chest X-rays of 78 patients. These patients with limited small cell lung cancer were treated from May 1980 to July 1983 in two consecutive alternating radiotherapy-chemotherapy schedules. Chest X-rays performed at each 6-month interval were read by each observer. A second reading was performed the day after. The analysis of results showed that in spite of some systematic variations in intra- and inter-observations, the proposed grading system had a good reproducibility. The radiological lung fibrosis score progressed between 6 and 12 months but was stable after one year of follow-up. There was no difference in the score of lung fibrosis between the two protocols which delivered a total dose of 45 and 55 Gy to the mediastinum. There was no significant correlation between the radiological changes and clinical symptoms.

Simultaneous high-dose external irradiation and daily cisplatin in unresectable, non-metastatic adenocarcinoma of the pancreas: a phase I-II study.

BACKGROUND AND PURPOSE: Clinical trials have demonstrated that high dose radiation therapy and daily cisplatin (CDDP) could increase local control and survival in carcinoma from various sites. The present phase I-II study has combined high dose radiation therapy and daily CDDP at escalating dosages. METHODS: From August 1994 to December 1995, 23 patients with non-resectable carcinoma of the pancreas were enrolled in a phase I-II multicentric, pilot study to test the toxicity and the effectiveness of high dose radiotherapy and daily cisplatin (CDDP) at escalating dosages. A dose of 6 mg/sqm/day of CDDP was selected for the phase II step since no grade IV toxicity occurred in any patient in the phase I step. RESULTS: Toxicity was considered fairly acceptable. At the time of analysis, the 23 patients who entered the study had clear evidence of evolutive disease either locally or distantly in the liver. It is suggested that high dose radiotherapy (60 Gy continuously) and daily CDDP have little effect on local control of the tumor and survival, and only a moderate effect on pain. CONCLUSIONS: In unresectable, apparently non-metastatic cancers of the pancreas, there is an urgent need for new agents or new combinations of agents to be tested.

Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial.

BACKGROUND AND PURPOSE: A 5 week-hyperfractionated and accelerated radiotherapy regimen without reduction of the total dose was developed to fight tumour repopulation during treatment and tumour hypoxia. The purpose of the study was to try to improve loco-regional control in high risk head and neck carcinoma treated with curative radiotherapy. METHODS AND MATERIALS: From 1985 to 1995, a randomised controlled trial of the EORTC Cooperative Group of Radiotherapy (EORTC 22851) compared the experimental regimen (72 Gy/45 fractions/5 weeks) to standard fractionation and overall treatment time (70 Gy/35 fractions/7 weeks) in T2, T3 and T4 head and neck cancers (hypopharynx excluded). The end-point criteria were local and loco-regional control, overall and disease-free survival, and acute and late toxicities. Five hundred twelve patients were accrued. RESULTS: Patients in the AF (accelerated fractionation) arm did significantly better with regard to loco-regional control (P = 0.02) resulting at 5 years in a 13% gain (95% CI 3-23% gain) in loco-regional control over the CF (conventional fractionation) arm. This improvement is of larger magnitude in patients with poorer prognosis (N2-3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent prognostic factor of good prognosis for loco-regional control (P = 0.03). Specific survival shows a trend (P = 0.06) in favour of the AF arm. ACUTE AND LATE TOXICITIES: Acute and late toxicity were increased in the AF arm. Late severe functional irradiation damage occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord. CONCLUSIONS: This trial shows that accelerated radiotherapy improves loco-regional control in head and neck squamous cell carcinomas. A less toxic scheme should, however, be investigated and documented before using accelerated radiotherapy as a standard regimen of curative radiotherapy for head and neck cancers.

Lymph node prognostic factors in head and neck squamous cell carcinomas.

BACKGROUND: This retrospective study included 914 patients who underwent a lymph node dissection at our institute between 1980 and 1985. The primary tumor sites were oral cavity, 287; hypopharynx, 249; larynx, 247; and oropharynx, 131. PATIENTS AND METHODS: On the basis of anatomic considerations, the sentinel nodes for well-lateralized oral cavity tumors were defined as homolateral levels I, II, and III; for oropharyngeal, hypopharyngeal, and laryngeal tumors, the sentinel nodes were defined as levels II and III. We took into account the ipsilateral side of the neck for well-lateralized tumors, and both sides for medium or large tumors. For clinically positive nodes of more than 3 cm, a radical neck dissection was performed. Other patients underwent a selective neck dissection on sentinel nodes, with immediate pathologic evaluation. Modified radical neck dissections with contralateral selective dissection were performed when frozen sections were positive. Patients with positive nodes were given postoperative radiotherapy. RESULTS: The prognostic factors studied, using the Cox survival model adjusted on the primary tumor site, surprisingly showed a nonsignificant value for extracapsular spread (P = 0.09), and a significant value for the number of positive nodes (P < 0.001) and for the positive node in or out of the sentinel node sites (P < 0.001). Although the node location factor can be used instead of positive node in or out of the sentinel node site, it has a less significant prognostic value. CONCLUSIONS: The most significant prognostic factors are the site of the positive node in or out of the sentinel node and the number of positive nodes; and a more accurate approach can be obtained by combining both factors. Node location in the upper or lower neck remains a substitute prognostic factor for the site of the positive node in or out of the sentinel node.