Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

Purpose: To study the efficacy of reirradiation as salvage treatment in patients with locally recurrent nasopharyngeal carcinoma. Patients and Methods: Between 1993 and 2000, 20 consecutive patients (twelve males and eight females) with nasopharyngeal cancer, previously irradiated in different Hungarian institutions, were reirradiated for biopsy-proven locally recurrent tumor. Histologically, 85% of the patients had WHO type III, 5% type II, and 10% type I disease. Stages I-IV (AJCC 1997 staging system) were assigned to five (25%), seven (35%), five (25%), and three (15%) patients, respectively; none of them had distant metastases, and only eight (40%) displayed regional dissemination. The median time period between termination of primary treatment and local recurrence was 30 (range, 10-204) months. Brachytherapy was the method most frequently used: in ten cases alone (especially for rT1 tumors), and in eight cases in combination with external beam therapy. Two patients with locally advanced disease underwent external beam therapy only. The median dose in the event of brachytherapy alone was 20 Gy (4 2 5 Gy or 5 2 4 Gy, range, 16-36 Gy), and the dose range for exclusive external irradiation was 30-40 Gy. In cases of combined irradiation, a median 20-Gy brachytherapy (range, 16-40 Gy) was associated with 30-40 Gy of external irradiation. Radiotherapy was supplemented by neck dissection (six patients), nasopharyngectomy (one patient), or chemotherapy (eleven patients). Results: 16 patients were reirradiated once, three twice, and one patient three times, with a median equivalent dose for tumor effect of 36 Gy (mean, 44 Gy; range, 19-117 Gy; the estimated !/#-ratio was 10 Gy). The median equivalent dose of reirradiation for late effect on normal tissue (with an estimated 70% delivery of the tumor dose) amounted to 30 Gy (mean, 37 Gy; range, 13-101 Gy, estimated !/#-ratio 3 Gy). After a median follow-up of 37 (range, 12-72) months, the overall survival was 60% (12/20). Seven of the twelve surviving patients are currently tumor-free. After primary irradiation, xerostomy occurred in all patients as an unavoidable side effect of treatment. Following reirradiation, a severe (grade 3 or higher) late toxicity (CTC criteria, version 2) has been observed in two tumor-free patients (10%) so far (necrosis of soft palate and paresis of glossopharyngeal nerve). Conclusion: Retreatment of nasopharyngeal carcinoma with radiotherapy (preferably a combined modality), can result in longterm local control and survival in a substantial proportion of patients, at the price of an acceptable morbidity. Ziel: Untersuchung der Effektivität einer Wiederbestrahlung als Palliativbehandlung bei Patienten mit lokal rezidivierendem nasopharyngealem Karzinom. Patienten und Methodik: Im Zeitraum von 1999 bis 2000 wurden 20 konsekutive Patienten (zwölf Männer und acht Frauen) mit nasopharyngealem Karzinom, die sich bereits früher in verschiedenen ungarischen Instituten einer Strahlentherapie unterzogen hatten, wegen eines bioptisch nachgewiesenen Rezidivtumors erneut bestrahlt. Histologisch gehörten 85% der Patienten dem WHO-Typ III, 5% dem Typ II und 10% dem Typ I an. Den Stadien I-IV (AJCC-Stagingsystem 1997) wurden fünf (25%), sieben (35%), fünf (25%) bzw. drei (15%) Patienten zugeordnet. Keiner der Patienten hatte Fernmetastasen, und nur acht (40%) zeigten eine regionale Disseminierung. Die mediane Zeitspanne zwischen Abschluss der primären Therapie und Auftreten des Lokalrezidivs betrug 30 (10-204) Monate. Die Brachytherapie wurde am häufigsten eingesetzt: in zehn Fällen allein (speziell für rT1-Tumoren) und in acht Fallen kombiniert mit einer externen Strahlentherapie. Zwei Patienten mit lokaler Krankheitsausbreitung wurden nur einer externen Strahlentherapie unterzogen. Die mediane Dosis betrug bei alleiniger Brachytherapie 20 Gy (4 2 5 Gy oder 5 2 4 Gy; Bereich 16-36 Gy). Der Dosisbereich für eine ausschließlich externe Bestrahlung lag zwischen 30 und 40 Gy. Bei kombinierter Bestrahlung war eine mediane brachytherapeutische Dosis von 20 Gy (Bereich 16-40 Gy) mit einer externen Bestrahlungsdosis von 30-40 Gy verbunden. Die Strahlentherapie wurde durch eine Neck-Dissection (sechs Patienten), Nasopharyngektomie (ein Patient) oder Chemotherapie (elf Patienten) ergänzt. Ergebnisse: 16 Patienten wurden einmal, drei zweimal und einer dreimal mit einer medianen tumorwirksamen Äquivalentdosis von 36 Gy (im Mittel 44 Gy, Bereich 19-117 Gy; geschätztes !/#-Verhältnis 10 Gy) wiederbestrahlt. Die mediane Äquivalentdosis der Wiederbestrahlung für den Späteffekt auf normales Gewebe (mit einer geschätzten Aufnahmerate von 70% der Tumordosis) lag bei 30 Gy (im Mittel 37 Gy, Bereich 13-101 Gy, geschätztes !/#-Verhältnis 3 Gy). Nach einer medianen Nachbeobachtungsperiode von 37 Monaten (Bereich 12-72 Monate) betrug die Gesamtüberlebensrate 60% (12/20). Sechs der zwölf überlebenden Patienten sind derzeit tumorfrei. Nach primärer Bestrahlung trat bei allen Patienten als unvermeidbare Nebenwirkung der Behandlung eine Xerostomie auf. Nach Wiederbestrahlung wurde bei zwei tumorfreien Patienten (10%) eine schwere (Grad 3 oder höher) Spättoxizität (CTC-Kriterien, Version 2) beobachtet (Nekrose des weichen Gaumens und Parese des Nervus glossopharyngeus). Schlussfolgerung: Die wiederholte Behandlung des nasopharyngealen Karzinoms mittels Strahlentherapie (vorzugsweise als kombinierte Modalität) kann bei einem beträchtlichen Patientenanteil in einer langfristigen lokalen Kontrolle und Überlebenszeit bei akzeptabler Morbidität resultieren.     

Reirradiation with local-field radiotherapy for painful bone metastases

PURPOSE: The purpose of this study was to evaluate retrospectively the effectiveness, prognostic factors, and sequelae of the first course of local-field reirradiation for painful bone metastases. PATIENTS AND METHODS: From 1994 to 2000, a total of 30 patients were reirradiated for painful bone metastases. The most commonly used initial treatment regimen was 30 Gy/10 Fr/2 wk. An additional dose in the range from 10 Gy/5 Fr to 26 Gy/13 Fr was reirradiated. RESULTS: Fifteen patients (50%) showed some type of pain relief after reirradiation. Patients with initial CR were more likely to respond than those with previous PR (100% vs. 41%). The median duration of pain relief was five months. The duration of response was longer in initial CR than initial PR. The median survival time of responders after retreatment was 11 months. No patient developed radiation myelopathy. Prognostic factors for pain relief were duration from initial treatment, performance status (PS), and status of bone metastases. CONCLUSION: Reirradiation for patients with a long duration from initial treatment (> or = 4 months), good PS (ECOG: 1-2), or solitary bone metastases was effective for pain relief. The appropriate indications, optimal dose, fractions, and technique for reirradiation to painful bone metastases should be further explored in randomized study.     

Reirradiation of Recurrent WHO Grade III Astrocytomas Using Fractionated Stereotactic Radiotherapy (FSRT)

PURPOSE: To assess the effect of reirradiation in recurrent WHO grade III astrocytomas. PATIENTS AND METHODS: From January 1995 to July 2003, 40 patients with grade III gliomas were treated with fractionated stereotactic reirradiation at the time point of recurrence. Median size of planning target volume for reirradiation was 56.2 ml (range 25.1-296.2 ml). A median target total dose of 36 Gy (range 20-57.6 Gy) was applied using a median fractionation of 5 x 2 Gy/week with a 6-MeV linear accelerator. RESULTS: Radiotherapy was well tolerated by all patients. No toxicities > CTC grade 2 developed. Median overall survival calculated from the time point of primary diagnosis was 48 months (range 7-180 months). The 5- and 10-year overall survival rates were 49.5% and 24.7%, respectively. From the time point of reirradiation, median survival was 16 months (range 1-98 months). Median progression-free survival from the time point of reirradiation was 8 months (range 1-72 months). No prognosticators for survival or progression-free survival after reirradiation could be identified. CONCLUSION: Fractionated stereotactic radiotherapy is well tolerated and effective in patients with recurrent grade III astrocytomas.     

Dose Escalation in Large Anterior Skull-Base Tumors by Means of IMRT

PURPOSE: To evaluate the feasibility and tolerance of dose escalation with stereotactic intensity-modulated radiotherapy (sIMRT) for skull-base tumors. PATIENTS AND METHODS: Between 01/2003 and 12/2004, twelve patients were treated. Nine were exclusively treated at the Novalis site with one planning target volume (PTV) field boost, three were administered boost IMRT treatment (two with each one PTV-shrinking field, one with single PTV) after conventional three-dimensional conformal radiotherapy. This resulted in 23 PTVs with a median volume of 93.63 cm3 (range, 88.58-125.88 cm3). Dose calculation was done by the pencil-beam algorithm. Median total doses of 66.6, 77.4, and 63.9 Gy were prescribed for sIMRT alone, sIMRT after 3-D conformal irradiation of the nasopharynx and cervical lymph nodes with 59.4 Gy, and for reirradiation, respectively. RESULTS: 95% isodose PTV coverage was reached in 86.5% (range, 80-93%). Homogeneity (Dmax/Dref) was 1.11, 1.09, and 1.08. Median total doses to 50% of chiasm, right and left optic nerve were 16.21, 16.82 and 10.23 Gy. 11/12 patients are locally controlled with a median follow-up of 11 months (range, 3-23 months), one has died of pulmonary embolism after cerebrospinal dissemination of retinal adenocarcinoma. CONCLUSION: SIMRT enables dose escalation to tumors located close to critical organs. Inverse planning for micro-multileaf collimator stereotactic irradiation is practicable in the daily routine irradiation program. SIMRT needs special verification and still, the following parameters have to be standardized: IMRT dose specification, dose maxima, length of radiation delivery time.     

Retrospective analysis of nasopharyngeal carcinoma treated during 1976-1985: late complications following megavoltage irradiation.

A retrospective analysis was undertaken of the late complications observed in 4527 patients with nasopharyngeal carcinoma treated by megavoltage radiotherapy during the years 1976-1985. Unconventional fractionation schedules were used because of serious resource limitations. The median equivalent doses were 65 Gy to the nasopharyngeal region and 53 Gy to the cervical region. 707 patients had reirradiation for local recurrences and 250 for regional relapses. The 10-year actuarial cancer-specific survival was 47%, and the corresponding all-complication-free and neurological-complication-free rates were 40% and 72%, respectively. Altogether, 1395 (31%) patients developed one or more late irradiation sequelae. The majority were mild soft-tissue damages, but 322 (7%) had significant functional disturbances, from which 62 (1%) died. Neurological damage that occurred in 450 (10%) patients constituted the major morbidity and accounted for all but three of the treatment mortalities. The cumulative incidence of the various complications is summarized, and the data recorded in the literature reviewed in order to give a proper perspective of the problem. Patients treated during 1981-1985 had a significantly higher actuarial encephalomyelopathy-free rate than those treated during 1976-1980, but the incidence-free rates for the other neurological complications remained unimproved, suggesting that the improvement could be mainly attributed to additional shielding for the brainstem rather than the reduction of dose from 3.8-4.2 Gy to 2.5 Gy per fraction.     

Analysis of prognostic factors in 106 cases of carcinoma of the rhinopharynx treated with cobalt teletherapy

A series of 106 patients affected with nasopharyngeal carcinomas and treated by definitive external irradiation from January 1975 to December 1986 was retrospectively reviewed. The median follow-up, from the end of the treatment, was 43 months (range 24-90). The nasopharynx received not less than 60 Gy to the midplane: the clinically negative neck (N0) was treated with a total dose of 50 Gy and the patients who had N1-3 disease received not less than 60 Gy. Thirty-eight patients had a recurrence in the irradiated areas (31 in the nasopharynx, and 7 in the neck); 17 patients developed distant metastases. Disease-free survival at 60 months was 42%. The most significant prognostic factor (p less than 0.05) was the presence of advanced neck involvement (N2-3), since most of the lymphatic and distant recurrences were observed in this group of patients. The overall results did not reveal but slight differences in the survival according to histology, even though patients with undifferentiated carcinomas had a local recurrence rate significantly lower than those with squamous cell carcinomas. Our findings suggest that patients with N2-3 neck diseases or with locally advanced involvement (T3-4) be treated by adjuvant chemotherapy in order to decrease the risk of local and distant relapses.     

Hyperfractionated Radiotherapy in Locally Advanced Nasopharyngeal Cancer

BACKGROUND: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. PATIENTS AND METHODS: 43 patients with nasopharyngeal cancer (stage II-IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. RESULTS: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. CONCLUSION: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.     

High-dose-rate interstitial brachytherapy for gynecologic malignancies

PURPOSE: The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB). METHODS AND MATERIALS: Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45 Gy (range, 39.6-50.4 Gy) with 11 patients receiving parametrial boost to a median dose of 9 Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed-Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75 Gy in five fractions delivered twice daily. The median followup was 25 months (6-69 months). RESULTS: Median cumulative biologic effective dose (EBRT+HDRB) to tumor volume was 78.9 Gy10 with the range of 72.5-85.2Gy10. Median cumulative biologic effective dose for the rectum and bladder were 99.4 Gy3 (range, 79.6-107.8 Gy3) and 96.4 Gy3 (range, 78.3-105.3 Gy3), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity. CONCLUSIONS: Our series suggests that single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach.     

Three-Dimensional Conformal or Stereotactic Reirradiation of Recurrent, Metastatic or New Primary Tumors

PURPOSE: To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques. PATIENTS AND METHODS: 108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy. RESULTS: Median follow-up was 7 months (range, 1-50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent. CONCLUSION: A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.     

Radiochemotherapy in Combination with Regional Hyperthermia in Preirradiated Patients with Recurrent Rectal Cancer

BACKGROUND AND PURPOSE: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. PATIENTS AND METHODS: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m(2)/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. RESULTS: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months] with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. CONCLUSION: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer.     

Radioactive needle implants in the treatment of anorectal cancer

Radioactive needle implants were used to treat 44 patients with inoperable anorectal cancer. An implant dose of 60 Gy or higher was administered to 27 patients at a mean dose rate of 0.493 Gy/h (SE +/- 0.167 Gy/h). In five patients this was preceded by external beam irradiation. A further 17 patients received an implant dose of less than 60 Gy; this followed external irradiation in 10 patients. A complete response was achieved in 52% (16 out of 31) of patients assessed. Three of these patients later relapsed locally. The median duration of response was 23 months. A partial response of median duration 3 months was achieved by a further 13 patients. Five year actuarial survival was 23.9%. Serious morbidity occurred in six patients; three developed strictures and three necrosis. Features of the tumour and the treatment technique contributing to successful management are discussed. It is suggested that radioactive needle implants have an important part to play in the management of low-lying inoperable anorectal cancers.     

High-dose-rate interstitial brachytherapy for vaginal endometrial cancer recurrence after prior surgery and radiotherapy

PurposeCharacterize the clinical outcomes of endometrial cancer vaginal recurrences after previous surgery and radiation therapy treated with reirradiation including image-guided interstitial high-dose-rate (HDR) brachytherapy.Methods and materialsA single-institution retrospective study identifying women receiving reirradiation for vaginal recurrence of endometrial cancer between 2004 and 2017.ResultsTwenty-three women had vaginal recurrences of endometrial cancer, median 13.7 months (range 3.5–104.9) from initial radiation. All received reirradiation with interstitial HDR brachytherapy, and seven also received external beam radiation. Median reirradiation EQD2_10 was 48 Gy (range 24.0–68.81), and median cumulative EQD2_10 was 106.25 Gy (range 62.26–122.0). Median follow-up after reirradiation was 40.2 months (range 4.5–112.7). At 3 years, overall survival was 56%, cancer-specific survival was 61%, and disease-free survival was 46%. 14 patients experienced disease recurrence; 10 including distant sites, one at a regional node only. Three patients experienced local recurrences, two of whom did not complete the prescribed course of reirradiation. The overall crude local control rate was 87%. Three patients experienced Grade 3 vaginal toxicity. There was no bladder or rectal toxicity with Grade >2.ConclusionsReirradiation including interstitial HDR brachytherapy is a promising option for vaginal recurrences of endometrial cancer after prior radiation, with high rate of local control and acceptable toxicity. However, distant failure is common. Further studies are needed to determine cumulative radiation dose limits and the role of systemic therapy in this scenario.     

Phase II trial of image-based high-dose-rate interstitial brachytherapy for previously irradiated gynecologic cancer

PurposeTo report the disease-free Grade ≥3 complication-free survival of a Phase II protocol of reirradiation with high-dose-rate (HDR) interstitial brachytherapy (ITB) in previously irradiated gynecologic cancer.Methods and MaterialsFifteen patients with previously irradiated cervical (n = 6), endometrial (n = 6), and vulvovaginal tumors (n = 3) were treated with HDR-ITB alone to a median dose of 38 Gy in 8 b.i.d. fractions over 4 consecutive days. Prior treatments included surgery (n = 12; 80%), external irradiation (n = 15; 100%), and brachytherapy (n = 9; 60%). Average clinical target volume Size was 60.9 cc (range, 14.8–165.3 cc), and median time to reirradiation was 3.9 years (range, 0.4–22.7 years).ResultsWith a median followup of 2.8 years (range, 1.2–9.2 years), 3 patients (20.0%) developed Grade ≥3 toxicity consisting of Grade 3 intestinal obstruction (n = 1), Grade 4 rectovesical fistula (n = 1), and Grade 5 intestinal obstruction (n = 1). Six patients remain alive and without evidence of disease at last followup. Two patients are alive with disease progression, and 7 patients have died, 4 of them from disease progression and 3 from other causes. The 2-year disease-free Grade ≥3 complication-free survival was 40%.ConclusionsHDR-ITB alone is a reasonable salvage treatment option in a significant number of patients with previously irradiated gynecologic tumors.     

Merkel Cell Carcinoma: The Role of Radiation Therapy in General Management

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant, locally aggressive tumor of the skin. Because few data exist about the clinical course of irradiated patients, we reviewed the 17 patients treated at our institution since 1982. PATIENTS AND METHODS: The median age at diagnosis was 71 years (range 47 to 88 years). Twelve patients presented with lymph node involvement (Stage II), 5 patients with negative lymph nodes (Stage I). Five patients were irradiated immediately after initial surgical excision of the primary tumor. Eleven patients underwent a surgical treatment of recurrence prior to the first irradiation. Only 1 patient received primary radiotherapy. A median dose of 52.8 Gy (range 40 to 60 Gy) in the region of the primary tumor and a median dose of 49.5 Gy (range 30 to 54 Gy) in the regional lymph nodes were delivered. RESULTS: The median overall survival after first diagnosis was 45 months. Three-year overall survival was 57%, 5-year cause-specific survival was 73% (Kaplan Meier). Local control could be achieved in the 5 patients irradiated immediately after surgical treatment of the primary tumor. In contrast, an in-field recurrence occurred in 5 of 12 patients irradiated after surgical excision of relapsed disease. Five patients developed distant metastases. None of these patients was irradiated immediately after surgical excision of the primary tumor. CONCLUSIONS: With respect to our experience, a local control can be achieved with an immediate postoperative radiotherapy of the primary tumor site and the adjacent lymph nodes.     

Reirradiation using high-dose-rate brachytherapy in recurrent carcinoma of uterine cervix

PurposeTo assess the feasibility of reirradiation with image-based high-dose-rate brachytherapy in previously irradiated patients with recurrent carcinoma of uterine cervix.Methods and MaterialsThirty previously irradiated patients diagnosed with central recurrence were treated with reirradiation. Martinez Universal Perineal Implant Template was used in 24 patients and Vienna applicator in 6 patients. Median interval between two radiation schedules was 25 months. Median delivered dose was 42 Gy equivalent dose at 2 Gy (EQD2; interquartile range, 37–46 Gy EQD2).ResultsAll 30 patients tolerated reirradiation well. Complete response was seen in 23 (76%) patients. With a median followup of 25 months, 2-year local control, disease-free survival, and overall survival were 44%, 42%, and 52%, respectively. Fifteen patients developed local recurrences; Local control rate was significantly higher with doses >40 Gy EQD2 (52% vs. 34%; p = 0.05). Disease-free survival was better for patients with longer interval (>25 months) between two radiotherapy schedules. Grade III radiation proctitis and cystitis was seen in 3 patients each, and Grade II small bowel toxicity was seen in 3 patients.ConclusionsReirradiation using high-dose-rate brachytherapy is feasible with acceptable outcomes in isolated local recurrence deemed unsuitable for surgery. The outcome is better with higher doses.     

Radiation therapy for life- or function-threatening infant hemangioma

PURPOSE: To assess the effectiveness and long-term results of radiation therapy in infants with life- or function-threatening hemangiomas. MATERIALS AND METHODS: Thirteen patients with life- or function-threatening hemangiomas (eight male, five female; age range, 0-8 months; median age, 2 months) were treated with radiation therapy. Life-threatening hemangiomas were treated with five fractions of radiation per week, and function-threatening hemangiomas were treated with two fractions per week. A median dose of 10 Gy was delivered to each hemangioma. The presence of residual hemangiomas, skin changes, functional problems, and growth delay was evaluated. RESULTS: All patients with Kasabach-Merritt syndrome (KMS) showed regression of the hemangioma and an increase in platelet counts to greater than 100,000 per cubic millimeter (1.0 x 10(11) per liter) within 40 days after radiation therapy. The treatment field was inadequate in two patients who required reirradiation or a change of treatment portal. With the exception of the patients with KMS, all but one patient experienced relief from symptoms in 40 days. Severe long-term radiation-related morbidity was noted in one patient who required reirradiation for a relapsed hemangioma. CONCLUSION: Radiation therapy (in doses of < or = 10 Gy in 2-Gy fractions) is indicated for life-threatening hemangiomas and for some function-threatening hemangiomas.     

Late Effects and Cosmetic Results of Conventional Versus Hypofractionated Irradiation in Breast-Conserving Therapy

BACKGROUND AND PURPOSE: Breast irradiation after lumpectomy is an integral component of breast-conserving therapy (BCT). As the prognosis is general good following BCT, late morbidity and cosmesis are important. The present study compares two different radiation schedules with respect to these two endpoints. PATIENTS AND METHODS: 129 breast cancer patients (pT1-2 pN0-1 cM0) were irradiated between 09/1992 and 08/1994 with either a 22-day fractionation schedule (2.5 Gy to 55 Gy, 4x/week, n = 65) or with a conventional fractionation schedule (28 days, 2.0 Gy to 55 Gy, 5x/week, n = 64), both without additional boost. The equivalent dose of 2-Gy fractions (EQD2) was 55 Gy and 62 Gy, respectively. Late toxicity, assessed according to the LENT-SOMA criteria, and cosmetic outcome, graded on a 5-point scale, were evaluated after a median of 86 months (range 72-94 months) in tumor-free breast cancer patients. RESULTS: LENT-SOMA grade 2/3 toxicity (2.5 Gy vs. 2.0 Gy): breast pain (18% vs. 11%; p = 0.3), fibrosis (57% vs. 16%; p < 0.001), telangiectasia (22% vs. 3%; p = 0.002), atrophy (31% vs. 3%; p < 0.001). Medication to breast pain was taken by 8% versus 9% of patients. Cosmesis was very good/good/acceptable in 75% versus 93% (2.5 Gy vs. 2.0 Gy; p = 0.006). CONCLUSION: Late morbidity was significantly frequent and cosmesis was significantly worse after hypofractionated radiotherapy (2.5 Gy to 55 Gy). However, morbidity was not associated with major implications on daily life.     

High-dose-rate endorectal brachytherapy for locally advanced rectal cancer in previously irradiated patients

PurposePreoperative high-dose-rate (HDR) endorectal brachytherapy is well tolerated among patients with locally advanced rectal cancer. However, these studies excluded patients who previously received pelvic radiation therapy (RT). Because a favorable toxicity profile has been published for HDR endorectal brachytherapy, we evaluated this technique in patients who have previously received pelvic irradiation.Methods and MaterialsWe included patients who had received pelvic irradiation for a previous pelvic malignancy and later received preoperative HDR endorectal brachytherapy for rectal cancer. Brachytherapy was delivered to a total dose of 26 Gy in 4 consecutive daily 6.5 Gy fractions.ResultsWe evaluated 10 patients who previously received pelvic external beam radiation therapy (EBRT) alone (n=6), EBRT and brachytherapy (n=2), or brachytherapy alone (n=2). The median interval between the initial course of RT and endorectal brachytherapy was approximately 11 years (range, 1-19 years). Two patients experienced a complete pathologic response while 1 patient had a near complete pathologic response. No acute grade ≥3 toxicity was observed. No intraoperative or postoperative surgical complications were observed.ConclusionsPreoperative HDR endorectal brachytherapy is an alternative to EBRT for patients with locally advanced rectal cancer who have previously received pelvic RT.     

Exclusive radiotherapy of locally advanced carcinoma of the larynx. Analysis of the caseload of Varese (1979-1986)

The authors analyse a retrospective series of 90 consecutive patients (pts) affected with locally advanced laryngeal carcinoma (T3-4, N0-3--TNM, UICC 1978) who were radically irradiated from November 1979 to December 1986 at the Radiotherapy Department of the General Hospital of Varese. All the patients were treated with 60Co and two opposed parallel lateral fields and progressive shrinkage: 66 with conventional fractionation (2 Gy once a day, 5 times a week), 24 with an accelerated hyperfractionated regimen (1.5 Gy twice a day, 5 times a week). The median total dose delivered to the tumor and clinically involved nodes was 64 Gy (1678 reu, CRE). Median follow-up was 21 months (range: 3-113). The 5-year overall survival (Kaplan-Meier) was 40.5%. The 5-year disease-free survival, for 47 patients in complete remission at the end of radiotherapy, was 51.9% after irradiation alone and 56.7% with salvage surgery. There were no statistically significant differences in survival according to local spread (T3 vs. T4), nodal status (N0 vs. N1-3) and dose fractionation regimen (conventional vs. accelerated hyperfractionated). Isoeffect (CRE) values above 1751 reu obtained a 3-year loco-regional control rate of 65%, while, for isoeffect values under 1600 reu, the 3-year loco-regional control rate was 33.3%. Relevant late sequelae were not observed. Our findings suggest that primary radiotherapy with salvage surgery in reserve could be considered as an effective choice for locally advanced laryngeal carcinoma, at least in selected groups of patients.     

Chemoradiation in Cervical Cancer with Cisplatin and High-Dose Rate Brachytherapy Combined with External Beam Radiotherapy Results of a Phase-II Study

BACKGROUND: In 1999, five randomized studies demonstrated that chemoradiation with cisplatin and low-dose rate (LDR) brachytherapy has a benefit in locally advanced cervical cancer and for surgically treated patients in high-risk situations. We evaluated the safety and efficacy of concomitant chemoradiation with cisplatin and high-dose rate (HDR) brachytherapy in patients with cervical cancer. PATIENTS AND METHODS: 27 patients were included in our phase-II trial: 13 locally advanced cases (group A) and 14 adjuvant-therapy patients in high-risk situations (group B). A definitive radiotherapy was performed with 25 fractions of external beam therapy (1.8 Gy per fraction/middle shielded after eleven fractions). Brachytherapy was delivered at HDR schedules with 7 Gy in point A per fraction (total dose 35 Gy) in FIGO Stages IIB-IIIB. The total dose of external and brachytherapy was 70 Gy in point A and 52-54 Gy in point B. All patients in stage IVA were treated without brachytherapy. Adjuvant radiotherapy was performed with external beam radiotherapy of the pelvis with 1.8 Gy single-dose up to 50.4 Gy. Brachytherapy was delivered at HDR schedules with two fractions of 5 Gy only in patients with tumor-positive margins or tumor involvement of the upper vagina. The chemotherapeutic treatment schedule provided six courses of cisplatin 40 mg/m2 weekly recommended in the randomized studies GOG-120 and -123. RESULTS: A total of 18/27 patients (66.7%) completed all six courses of chemotherapy. Discontinuation of radiotherapy due to therapy-related morbidity was not necessary in the whole study group. G3 leukopenia (29.6%) was the only relevant acute toxicity. There were no differences in toxicity between group A and B. Serious late morbidity occurred in 2/27 patients (7.4%). 12/13 patients (92.3%) with IIB-IVA cervical cancer showed a complete response (CR). 13/14 adjuvant cases (92.8%) are free of recurrence (median follow up: 19.1 months). CONCLUSION: Concomitant chemoradiation with cisplatin 40 mg/m2 weekly x 6 using HDR brachytherapy represents a promising treatment of cervical cancer with an acceptable toxicity.