Alejandro de la Torre

Phase II study of radiochemotherapy with uft and low-dose oral leucovorin in patients with unresectable rectal cancer

PURPOSE To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer. METHODS AND MATERIALS Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m2/day UFT and 30 mg/day leucovorin on days 8-35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy. RESULTS Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%). CONCLUSION The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.

Incidence of human papillomavirus-related oropharyngeal cancer and outcomes after chemoradiation in a population of heavy smokers

Incidence of human papillomavirus (HPV)‐related oropharyngeal carcinomas is increasing worldwide. The purpose of this study was to report the incidence in our region, and to determine the influence of HPV status on survival among a heavy smoking population.

Salvage brachytherapy and salvage surgery for recurrent oropharyngeal carcinoma following radiotherapy

We reviewed 21 patients who underwent salvage treatment after a biopsy of proven locally recurrent carcinoma of the oropharynx. Two of these patients underwent a second salvage treatment after failure of the first. Treatment was performed with Ir192 interstitial implant in 17 cases (13 rT1 and 4 rT2); by surgery in five cases (3 rT1, 1 rT2, 1 rTx), including two patients who had relapsed after salvage treatment with Ir192 implant; and by hyperfractionated external beam irradiation plus concomitant Tegafur chemotherapy in one case (rT3). The primary tumour was controlled in four of the 17 cases (23 per cent) treated with Ir192 implant. Of these four patients, two remained disease-free 42 and 59 months after treatment, one died of nodal metastases eight months after treatment and another of distant metastases 19 months after treatment. Four of the five cases (80 per cent) treated with surgery, including two patients who relapsed after salvage brachytherapy, remained free from local, regional and distant relapse 21, 25, 31 and 56 months after treatment.

Episcleral iridium-192 wire therapy for choroidal melanomas.

PURPOSE To evaluate the effectivity of high-dose episcleral iridium-192 wires in the treatment of choroidal melanoma. METHODS AND MATERIALS In 1983, the Departments of Radiation Oncology and Ophthalmology at the Clínica Puerta de Hierro, Madrid, Spain, initiated a clinical study using removable episcleral iridium-192 wires in the treatment of choroidal melanoma. Sixty-six evaluable patients were treated from January 1983 through July 1992. Two patients had a small sized tumor (3%), 28 had a medium sized tumor (42%), and 36 patients had a large tumor (54%). The mean follow-up was 40 months (6-118 months). The dose to the apex of the tumor ranged from 66 to 97 Gy (mean 76.6 Gy), and the doses at 2 mm depth ranged from 77 to 433 Gy (mean 200 Gy). RESULTS Tumor regression or stabilization was observed in 53 of the 66 patients (90%). Visual acuity improved following treatment in 5 out of 54 patients (9%), remaining unchanged in 30 out of 54 (56%), and decreased in 19 out of 54 (35%) patients. The remaining seven patients had undergone enucleation. Late complications have been documented in 20 out of 66 patients (30%), including 6 patients in whom enucleation was required because of radiation-related complications. The probability of survival and survival free of local progression was 93% at 5 years and 79% at 10 years. The probability of retaining the treated eye is 82% after the fifth year posttreatment. CONCLUSIONS Treatment of choroidal melanomas with episcleral iridium-192 wires is as effective as treatment with other radioactive applications. We feel that our results using iridium-192 wires are comparable to the other methods. However, we think that our technique is simple to implement, relatively inexpensive, and well tolerated.

Prognostic Factors in Hodgkin's Disease

Hodgkins disease (HD) is a curable tumoral disease. However, there are groups of patients who suffer relapse and the identification of prognostic factors and the adaptation of treatments to individual risk is one the lines of investigation in this disease. A study was performed on 526 patients diagnosed of HD in our hospital between January 1967 and September 2001. An analysis was made of the most important variables in terms of both disease-free and overall survival. Overall survival in this series of patients was 94% at 2 years, 86% at 5 years, 76% at 10 years and 72% at 15 years. Median survival was 249 months. Factors influencing poor prognosis in the overall survival were: male gender (P < 0.0001), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.0001), B symptoms (P < 0.0001), spleen involvement at diagnosis (P = 0.003), no complete remission after first line treatment (P < 0.0001), and more than 30 years-of-age (P < 0.0001). Disease free survival was 83% at 2 years and 68% at 5 years although without reaching the mean follow-up. The disease free survival study revealed the following risk factors: male gender (P = 0.02), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.001), B symptoms (P < 0.001), extranodal or splenic involvement (P < 0.05), and no complete remission after first line treatment (P < 0.0001). The result of treatment optimization is that some factors that were considered to indicate a poor prognosis have disappeared, and that others which are useful have appeared and allow us to establish groups with differing risks of relapse and who could be candidates for differentiated treatments.

Influence of Boost Technique (External Beam Radiotherapy or Brachytherapy) on the Outcome of Patients with Carcinoma of the Base of the Tongue

We reviewed 90 patients with squamous cell carcinoma of the base of the tongue. Fifty-three patients were treated with external beam radiotherapy alone (3 T1, 11 T2, 21 T3, and 18 T4 tumors) and thirty-seven patients were treated with external beam radiotherapy plus brachytherapy boost (4 T1, 15 T2, 11 T3, and 7 T4 tumors). For patients with T1, T2 and T3 primaries, the actuarial 3-year local relapse-free survival was 42% following external beam radiotherapy alone and 67% following external beam radiotherapy plus brachytherapy (p < 0.05). The actuarial 3-year cause specific survival for these T-stages was 37% for patients treated with external beam radiotherapy alone and 53% for patients treated with external beam radiotherapy plus brachytherapy (p = 0.1). In the Cox multivariate analyses restricted patients with T1, T2 and T3 staged tumors, treatment modality was the only predictor for local control but no influence on specific survival was found. The trend towards significant differences in specific survival found in the univariate comparison of both treatment modalities was probably due to the significantly higher number of N-positive patients treated with external beam radiotherapy alone. When all stages were included in the Cox analysis, low hemoglobin level, invasion of deep muscle, number of palpable nodes, and history of weight loss significantly influenced the outcome. Soft tissue necrosis occurred more frequently in patients treated with external beam radiotherapy plus brachytherapy (33% vs. 10%, p = 0.52).

Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature

PURPOSE To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkins disease (IDHD). METHODS AND MATERIALS During the period 1965-1997, 847 patients with early stage Hodgkins disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.

Cerebellar involvement in Hodgkin's lymphoma: an atypical site of relapse

The presentation of intracranial metastases from Hodgkin’s lymphoma is an infrequent event that worsens clinical outcome. A case of Hodgkin’s lymphoma relapse in the cerebellum is described in a 70-year-old woman with a previously treated stage IVA Hodgkin’s lymphoma. Diagnostic workup and treatment strategies for central nervous system relapses are reviewed and discussed. A combination of surgery, radiotherapy and occasionally chemotherapy remains the most appropriate approach to intracranial Hodgkin’s lymphoma.

Toxicity and compliance with a chemoradiotherapy schedule for advanced nasopharyngeal carcinoma: A single institution experience using the Intergroup 0099 study regimen

As the results of the Intergroup 0099 study showed a marked improvement in survival using concurrent chemoradiotherapy (c-CRT) and adjuvant chemotherapy (a-CT) in patients with locally advanced nasopharyngeal carcinoma (NPC), several groups now recommend this combined treatment as the standard form of care. Since November 1998, we have treated 23 patients with non-metastatic advanced NPC with the schedule used in the Intergroup 0099 trial. The patients and treatment characteristics are summarized in Table I. Here we describe a high rate of acute toxicity experienced at our institution using the regimen. Mucositis, hematological toxicity, and emesis were the main limiting adverse effects compromising total regimen compliance. In our series, only 4 (17%) out of 23 patients completed the 6 chemotherapy cycles as planned, 39% completed the concurrent chemotherapy, and 39% received three courses of a-CT, in contrast with 63% and 55% reported in the Intergroup study, respectively. These differences are explained by the higher incidence of grade 3 /4 mucositis and leukopenia presented in our group during the c-CRT compared with that reported in the Intergroup study (87% and 43% vs. 37% and 29% respectively). Other authors have also reported low compliance and a higher toxicity incidence with this regimen. Bahl et al. [2] treated 75 patients with locally advanced NPC, and found that only 43% of the patients received three cycles during c-CRT and 61% received all three cycles of a-CT, with only 33% receiving the intended dose intensity without modifications. Lee et al. [3] reported on 348 patients randomized to radiotherapy alone or chemoradiotherapy and found a higher incidence of acute toxicity in the chemoradiotherapy arm, with fatal toxicities ocurring in 2 patients. Despite the low compliance, the 2.8-year progression-free survival and overall survival obtained in our group (78% and 84%, respectively) are comparable to that obtained at 3 years in the chemoradiotherapy arm of the Intergroup study (69% and 78%, respectively). This could be related to a higher percentage (61%) of WHO type III histology in our series compared with 41% in the Intergroup study. Moreover, all 23 patients received at least 2 cycles during the c-CRT phase, and there is evidence that only the addition of concurrent chemotherapy to radiotherapy offers a small but significant effect on overall survival, and no survival benefit has been consistently demonstrated for the a-CT [4 /6]. In conclusion, we recommend careful and judicious selection of the chemotherapy schedule to avoid extreme toxicity and jeopardizing compliance with the complete treatment plan. Other chemoradiotherapy schedules using cisplatin-based c-CRT have been tested in randomized trials and are available with a better toxicity profile [7,8]. In our