Neoadjuvant Radiochemotherapy in Locally Advanced Gastric Carcinoma

BACKGROUND AND PURPOSE: Gastric carcinoma is characterized by a high rate of local recurrences and distant metastases and is often not resectable due to locally advanced stage. The aim of this study was to examine feasibility and effectiveness of neoadjuvant radiochemotherapy (RCT) for locally advanced, primarily nonresectable gastric carcinoma and to achieve curative resection. PATIENTS AND METHODS: 21 patients with locally advanced gastric cancer located in cardia (n = 17) and corpus (n = 4; seven cT3; 14 cT4; 18 cN+; all cM0) with a median age of 61 years were scheduled to receive neoadjuvant RCT. Therapy consisted of a conventionally fractionated, conformal radiotherapy using the shrinking-field technique (1.8 Gy to 45 Gy + 5.4 Gy) and chemotherapy using cisplatin (20 mg/m(2), d1-5, 29-33), 5-fluorouracil (5-FU; 800 mg/m(2), d1-5, 29-33) or paclitaxel (135 mg/m(2), d1, 29). 4-6 weeks after completion of RCT, surgery was performed whenever feasible. RESULTS: Hematologic toxicity was moderate with grade 3 leukopenia in 10/21 patients and grade 3 thrombopenia in 5/21 (CTC). Nonhematologic toxicities consisted of 5/21 cases of fever as well as one fungal sepsis. Following RCT, tumors were classified resectable in 16/21 patients (76%); 12/21 patients (58%) were operated on, 11/12 achieved clear margins (R0). Response was as follows: complete remission (CR) 3/21 (14%), partial remission 13/21 (62%), no change 3/21 (14%), systemic progressive disease (PD) 2/21 (10%). The median survival and the 2-year survival rates were 18 months and 42%, respectively, for the patients following R0 resections as compared to 10 months and 0% for the remaining patients (p = 0.035). Local control (4 years) for patients following R0 resection was 89%. CONCLUSION: Neoadjuvant RCT is feasible and locally highly effective but must be further investigated involving a higher number of patients.     

Concurrent Radiochemotherapy with Vinorelbine plus Cisplatin or Carboplatin in Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC) and an Increased Risk of Treatment Complications

BACKGROUND: In elderly patients, patients with multiple morbidities, and patients with a reduced general condition, the standard treatment of inoperable non-small-cell lung cancer (NSCLC) consists of either chemotherapy or radiation therapy alone and is associated with an extremely poor prognosis. We therefore investigated the feasibility, toxicity, and efficacy of radiotherapy with concurrent chemotherapy using vinorelbine plus cisplatin or carboplatin in NSCLC patients at risk for treatment complications. PATIENTS AND METHODS: A total of 33 patients (six women, 27 men, median age 65 years) with locally advanced, functionally inoperable pulmonary carcinomas, recurrent lung cancer or postoperative macroscopic residual tumors (R2) with an increased risk of treatment complications (WHO performance status 2/3; cardiac, renal or pulmonary failure; marked pretherapeutic weight loss; age between 71-75 years) received 12.5 mg of vinorelbine per m(2) body surface area (BSA) on days 1, 8, 15, 29, 36 and 43 plus either cisplatin 20 mg/m(2) BSA (ten patients) or carboplatin 70 mg/m(2) BSA (23 patients) on days 1-5 and 29-33 together with conventionally fractionated radiotherapy. The tumor regions were irradiated with doses of up to 63 Gy (90% isodose), and potentially affected lymph nodes received doses of up to 45.0 or 50.4 Gy (90% isodose). RESULTS: Briefly, 31 of 33 patients successfully completed radiation therapy and 26 received four cycles of vinorelbine plus at least two cycles of cisplatin or carboplatin. Hematotoxic side effects included grade III leukocytopenia (n = 8), grade III thrombocytopenia (n = 5), and grade IV thrombocytopenia (n = 2). Other side effects consisted of peripheral neuropathy grade III (n = 1) and esophagitis grade IV (n = 1). Severe pneumonitis did not occur. Six patients had pneumonia before radiochemotherapy. 21 patients (63%) exhibited a complete (n = 7) or partial response (n = 14) to chemoradiation. The twelve nonresponders had either stable (n = 9) or progressive disease (n = 3). The survival rates plus standard deviations were as follows: 1-year survival: 60 +/- 8%, 2-year survival: 36 +/- 9%, 3-year survival: 24 +/- 9%, median survival time: 17 months (5;29 months; 95% confidence interval [CI]), median progression-free survival: 11 months (9;13 months; 95% CI). The median follow-up time was 14 months. CONCLUSION: Conventionally fractionated radiochemotherapy with vinorelbine plus a platinum derivative is feasible in patients with NSCLC and increased risk of treatment complications. Compared to patient populations described in the literature, the survival rates achieved by concurrent radiochemotherapy appear to be better than those achieved with radiotherapy alone.     

6-Year Experience of Concurrent Radiochemotherapy with Vinorelbine Plus a Platinum Compound in Multimorbid or Aged Patients with Inoperable Non-Small Cell Lung Cancer

BACKGROUND AND PURPOSE: Although poor-risk patients represent no minority in inoperable non-small cell lung cancer (NSCLC), there is little experience with concurrent radiochemotherapy (RCT) in this group. Here, the authors report on the feasibility and efficacy of RCT with vinorelbine plus carboplatin or cisplatin in NSCLC patients with comorbidities and poor general health or advanced age. PATIENTS AND METHODS: A total of 66 patients (ten women, 56 men, median age 68 years) with inoperable NSCLC and an increased risk of treatment side effects (WHO performance score of 2-3; cardiac, pulmonary or renal failure or extensive weight loss before treatment, or an age of 71-78 years) were treated with vinorelbine 12.5 mg/m(2) on days 1, 8, 15, 29, 36, and 43 in combination with either carboplatin 70 mg/m(2) (n = 59) or cisplatin 20 mg/m(2) (n = 7) on days 1-5 and 29-33 in addition to receiving conventional fractionated radiotherapy with doses of up to 63 Gy (90% isodose). RESULTS: 62 of 66 patients (94%) reached the 90% level of the prescribed radiation dose, and 41/66 patient (62%) received at least two cycles of the platinum compound and four cycles of vinorelbine. The following hematologic side effects (CTC classification [Common Toxicity Criteria]) were observed: grade 3 (12%) and grade 4 (15%) thrombocytopenia, grade 3 (38%) and grade 4 (4%) leukocytopenia, and anemia requiring transfusion (26%). Other side effects (CTC) included grade 3 (3%) and grade 4 (2%) esophagitis and grade 3 pneumonitis (3%). The response rates were as follows: complete remission 18%, partial remission 56%, stable disease 21%, and progressive disease 5%. The cumulative survival rates were 53%, 24%, and 8% at 12 months, 24 months, and 5 years, respectively. CONCLUSION: After including a larger group of patients than in 2003 and following the patients for several years, the authors determine that concurrent RCT consisting of vinorelbine plus a platinum compound and conventional fractionated radiotherapy can be carried out with manageable toxicity, even in this negatively selected population of patients. Their survival rates were comparable to those achieved in other studies with simultaneous RCT.     

Intraoperative Radiotherapy of Soft Tissue Sarcoma of the Extremity

PURPOSE: Evaluation of treatment outcome after intraoperative radiotherapy (IORT) +/- external-beam irradiation (EBRT) in patients with localized soft tissue sarcoma of the extremity at high risk for local recurrence after limb-sparing surgery. PATIENTS AND METHODS: 28 patients treated between 1989 and 1999 were evaluated retrospectively. Patients presented with locally recurrent (n = 17), T2 (n = 20), high-grade (n = 26), or incompletely resected tumors (n = 11). All patients underwent limbsparing surgery and IORT (median dose of 15 Gy) given either with high-dose-rate brachytherapy or a linear accelerator. 25 patients received additional EBRT with a mean of 50.6 Gy (range: 30.6-60 Gy). The mean follow-up time was 4.3 years (95% confidence interval [CI]: 3.0-5.6 years). RESULTS: The 5-year overall and distant disease-free survival rates were 66% and 54%, respectively. The overall actuarial recurrence rate after 5 years is 16% (95% CI: 1%, 31%). The crude rate after 8 years is 18%. Surgical margin status, primary versus recurrent tumor and tumor stage did not show any statistically significant influence (univariate analysis) on local recurrence rates. Patients with T1 tumors exhibited a borderline significant (p = 0.053) better distant disease-free survival (83%) compared to T2 tumors (43%). Five (24%) grade 3-4 late side effects were observed. CONCLUSION: In patients with high-risk soft tissue sarcomas, IORT +/- EBRT after limb-preserving surgery achieves high local control rates. The risk of normal tissue toxicities is comparable to conventional limb-sparing treatment.     

Sites of Failure in Breast Cancer Patients with Extracapsular Invasion of Axillary Lymph Node Metastases

BACKGROUND AND PURPOSE: Extracapsular spread (ECS) is frequent, but the specific sites of relapse are seldom given in the literature. In this study it was evaluated, if ECS might be an indicator for axillary irradiation. PATIENTS AND METHODS: After a retrospective review of pathology reports, the information about ECS was available in 254 lymph node-positive patients: ECS was absent in 34% (ECS-negative; n = 87) and present in 66% (ECS-positive; n = 167). All patients were irradiated locally, 78 patients got periclavicular and 74 axillary irradiation (median total dose: 50.4 Gy). 240/254 patients (94.5%) received systemic treatment/s. Mean follow-up was 46 months. RESULTS: The regional relapse rate was 4.6% without ECS versus 9.6% with ECS. The 5-year axillary relapse-free survival was 100% in ECS-negative and 90% in ECS-positive patients (p = 0.01), whereas corresponding values for periclavicular relapse-free survival (with ECS: 91% +/- 4%; without ECS: 94% +/- 3%; p = 0.77) and local relapse-free survival (with ECS: 86% +/- 4%; without ECS: 91% +/- 3%; p = 0.69) were not significantly different. chi(2)-tests revealed a high correlation of ECS with T-stage, number of positive lymph nodes and progesterone receptor status, comparisons with estrogen receptor, grade, or age were not significant. In multivariate analysis number of positive lymph nodes was solely significant for regional failure. Dividing the patients into those with one to three and those with four or more positive lymph nodes, ECS lost its significance for axillary failure. CONCLUSION: ECS was accompanied by an enhanced axillary failure rate in univariate analysis, which was no longer true after adjusting for the number of positive lymph nodes.     

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.     

20 Years of Experience in Static Intensity-Modulated Total-Body Irradiation and Lung Toxicity

PURPOSE: To analyze lung complications after allogeneic or autologous transplantation following total-body irradiation (TBI) with compensators, so-called sIMRT (static intensity-modulated radiotherapy). PATIENTS AND METHODS: Between 1983 and 1998, 257 patients with different hematologic malignancies underwent TBI in six fractions to a total dose of 12 Gy within 3 consecutive days (212 with 11 Gy lung dose) prior to allogeneic (n=174) or autologous (n=83) transplantation. 40 patients were <16 years of age. Minimum follow-up time was 5 years. Median follow-up period was 110 months (13-231 months). RESULTS: 5-year survival rate was 47.9%, 5-year tumor-related mortality 23%, 5-year treatment-related mortality 29.2% (12 Gy lung dose: 53.3%+/-14.6%, 11 Gy: 24.1%+/-5.7%). Interstitial pneumonitis (IP) developed in 28 of 257 patients (10.9% +/- 3.8%). IP incidences in the allogeneic and autologous groups were 14.4% (+/-5.6%) and 3.6% (0-7.6%), respectively. IP incidences with 12/11 Gy lung dose were 22% (+/-12%)/8.5% (+/-3.7%). IP mortality was 9.3% (+/-3.6%). 13 of 28 patients with IP had a cytomegalovirus infection, five an acute graft-versus-host disease grade IV of the lungs. IP incidences with 12/11 Gy lung dose were 25% (9-50%)/4.2% (0.2-19.1%) in patients <16 years, and 20.7% (9.4-37.4%) and 13.3% (+/-6.5%) in older patients after allogeneic transplantation. CONCLUSION: Compensator-generated static intensity-modulated TBI with a total dose of 12 Gy and a lung dose of 11 Gy is a modern and comfortable treatment with moderate lung toxicity, small dose inhomogeneities and little setup failure before transplantation. Especially patients <16 years of age benefit from lung dose reduction.     

Adjuvante simultane Radiochemotherapie nach operiertem Uteruszervixkarzinom in der High-Risk-Situation Ergebnisse einer Pilotuntersuchung

BACKGROUND: The most important factors for prognosis of cervical cancers are age and histological criteria such as the tumor size, the involvement of lymph nodes, lympho-vascular space involvement as well as microvessel involvement and poor tumor differentiation (grading 3). Here we present the results of concomitant chemo-radiation at high-risk situation of patients with cervical cancer after surgery. PATIENTS AND METHODS: The study comprised 34 patients with median age of 40 years (26-63 years) after Wertheim surgical technique for cervical cancer at the FIGO Stages IB (n = 19) and IIB (n = 15). All patients were treated between November 1995 and June 1999 by a schedule of concomitant chemoradiation. The indication for this treatment was given by the positive histological proof of lymph node metastasis, microvessel or lympho-vascular space involvement as well as a G3 grading. The chemo-therapy was given in week 1 and 5 (day 1-5 and day 29-33). The dosage of cisplatin was 20 mg/m2/d on every day and 5-FU was given as a 120-h infusion with 600 mg/m2/d. The external beam radiotherapy was applied to the pelvis with 1.8 Gy per fraction up to 50.4-54 Gy. In two patients the paraaortal region was irradiated too because of the involvement of these lymph nodes. RESULTS: The median observation time was 48 months (3-68 months). 30 patients are alive (88%) in complete response. Four patients died. The mean survival was 61 +/- 3 months. We have seen only slight acute toxicities of grade 1 and 2. Three patients suffered from a grade 3 diarrhea and three patients developed a grade 3 leukopenia. In seven patients we found a secondary lymphedema as a late toxicity. CONCLUSION: The concomitant chemoradiation containing cisplatin in high-risk situation for cervical cancer after surgery improves the outcome and survival in these patients.     

Stereotactic Radiotherapy of Targets in the Lung and Liver

BACKGROUND: Stereotactic irradiation of extracranial targets offers a non-invasive treatment modality for patients with localized tumors, which are not amenable for surgery or other invasive approaches because of age or impaired medical condition. The purpose of the study was the evaluation of the method to achieve local control of irradiated targets in relation to treatment toxicity. PATIENTS AND METHODS: Irradiation was performed as hypofractionated treatment in three fractions of 10 Gy each, normalized to the PTV enclosing 65% isodose with patient fixation in a stereotactic body frame. The isocenter was localized by stereotactic coordinates. Targets were circumscribed tumors in the lung (n = 27) and liver (n = 24) not amenable for other treatment modalities: primary lung cancer (n = 12), local recurrences of lung cancer (n = 4), lung metastases (n = 11), liver metastases (n = 23) and one cholangiocellular carcinoma. Median CTV/PTV for targets in the lung was 57/113 cm3 (min/max 5-277 cm3/17-343 cm3) and for targets in the liver 50/102 cm3 (min/max 9-516 cm3/42-772 cm3). Median follow-up for targets in the lung was 8 months (2-33) and 9 months (2-28) for liver targets. Local control was defined as complete or partial remission and stable disease, measured by repeated CT scans after 6 weeks and in 3 months intervals. Treatment toxicity was evaluated according to the WHO score. RESULTS: Crude local control was 85% for pulmonary targets and 83% for hepatic targets. Actuarial local control after 1 and 2 years was 76% and 76% for lung tumors and 76% and 61% for liver tumors. Actuarial overall patient survival was 48% after 1 year and 21% after 2 years for targets in the lung and 71% and 43% for targets in the liver. No acute grade 3-5 side effects were observed. Serious late toxicity occurred in two patients: a chronic ulceration of the esophagus at a target close to the mediastinum after 3 months (grade 3) and fatal bleeding from the pulmonary artery after 9 months (grade 5) in a previously irradiated patient. It remained unclear, whether the bleeding was a side effect of irradiation or due to tumor infiltration. CONCLUSION: Hypofractionated stereotactic irradiation of targets in the lung and liver is a locally effective treatment with actuarial local control rates of 76% after 1 year and 61-76% after 2 years without relevant acute toxicity. Severe late toxicity did not occur, if targets close to the mediastinum were avoided.     

Surgical and radiotherapeutic treatment in stage I endometrial adenocarcinoma. Retrospective analysis of 218 patients

From April 1977 through April 1985, 218 stage I endometrial carcinomas were treated with radiosurgery or radiotherapy alone. Postoperative irradiation was external (60Co) in 131 and curietherapy in 27 patients. Twenty patients underwent preoperative curietherapy and 40 patients radiotherapy alone. Median follow-up was 5.6 years (range 3-11). The overall 5-year actuarial survival (Kaplan-Meier method) was 86.1% +/- 2.5. The 5-year D.F. actuarial survival was 95% +/- 4.9, 93.1% +/- 4.7, 88.4% +/- 2.9, respectively, for preoperative radiotherapy, postoperative curietherapy and postoperative external irradiation groups. The 5-year actuarial survival was 69.8% +/- 7.7 in the radiotherapy alone group. There was difference in survival among patients treated with radiotherapy alone as compared to those radiosurgically treated (P less than 0.001). Local and general recurrence rate was 8.2%; vaginal recurrences 2/218 (0.9%); pelvic recurrences 7/218 (3.3%); distant metastases 9/218 (4.1%). Overall side effects were observed in 20/218 patients (9.1%): grade I and II in 8.6% of cases, grade III in 0.9% of cases. The authors conclude that good results can be achieved with adjuvant radiotherapy both in high risk cases and in low risk cases, with minimal side effects.     

Aggressive Simultaneous Radiochemotherapy with Cisplatin and Paclitaxel in Combination with Accelerated Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Tumors

BACKGROUND: Simultaneous radiochemotherapy (sRCT) is the treatment of first choice in locally advanced head and neck cancers. We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. PATIENTS AND METHODS: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m(2) on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m(2) twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 +/- 61 cm(3). The mean follow-up was 30 months (range 4-39 months). RESULTS: One early death (peritonitis and sepsis at day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m(2) paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m(2) twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30 of neutropenic infection. In one patient, a grade 2 nephrotoxicity appeared requiring cessation of cisplatin chemotherapy. 18/23 patients (78%) required blood transfusion (1-3 units) and 16/23 (70%) i.v. antibiotics. 14 patients (61%) achieved a complete and nine (39%) a partial remission, yielding an overall response rate of 100%. In summary, six patients died of local tumor progression (n = 2), distant metastases (n = 2), or therapy-related complications (n = 2) during follow-up. The 3-year overall survival was 71%. Tumor volume was not a risk factor for failure in this protocol (mean tumor volume in relapse-free vs. progressive patients 71 +/- 65 cm(3) vs. 64 +/- 38 cm(3)). All patients have, so far, developed only slight late effects (fibrosis, lymphedema) with no grade 3-4 late sequelae. CONCLUSIONS: This very aggressive sRCT protocol yielded excellent response and survival figures but was associated with a very high rate of acute toxicity (8% therapy-related deaths). A maximal supportive treatment is therefore required.     

Radiation therapy for the esophageal carcinoma: external irradiation versus high-dose rate intraluminal irradiation.

From September 1977 through December 1989, 149 patients with esophageal carcinoma were treated with external irradiation (EI) with or without high-dose rate intraluminal irradiation (HDRII) using remote afterloading system. Two-year relapse-free survival rates were 52% in sage I (n = 23), 24% in stage II (n = 61) and 19% in stage III (n = 65). Two-year survival rates were 66% in complete response (CR) group (n = 65) and 7 to 9% in non-CR group (n = 84). Concerning CR group external irradiation alone (mean +/- S. D.: 66.5 +/- 5.2 Gy) showed higher local control rate than EI (60.0 +/- 0.4 Gy) + HDRII (10 Gy) (30/38 versus 15/27, p = 0.044), especially in ulcerative type (17/19 versus 5/11, p = 0.009). This preliminary result suggests that HDRII is not effective for the local control of the ulcerative lesion as a boost therapy.     

Radiotherapy of testicular seminoma. Stages I and II A, B

From June 1977 through June 1987, 46 patients (36 evaluable) affected by stage I and II non-bulky testicular seminoma were treated with postoperative telecobaltotherapy (TCT). In stage I seminomas, radiotherapy was extended to the omolateral iliac and the para-aortic areas (total dose: 30 Gy over 4 weeks). In stage II seminomas, the subdiaphragmatic lymph nodes were irradiated with 40-45 Gy over 5-6 weeks; after an interval of one month the subdiaphragmatic lymph nodes were irradiated again with a total dose of 25 Gy over 3.5 weeks. Minimal follow-up lasted two years and maximum ten years (average: 5.5). Two (5.5%) recurrences occurred, but salvage radiotherapy and salvage chemotherapy respectively allowed a complete permanent remission. One patient died from a different neoplasia with no evidence of testicular involvement. The 5-year actuarial survival is 96.6 +/- 3.4. In 20% of the patients the side effects were nausea and/or vomiting, easily controlled. No late complications were observed.     

Simultaneous radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in advanced head and neck tumors]

Between 1.1. 1987 and 31.12. 1988 47 patients with locally advanced head- and neck tumours (UICC-stage II: one patient, stage III: 16 patients, stage IV: 30 patients) were treated with simultaneous radio-chemotherapy. Localisations were hypopharynx (23 = 49%), oropharynx (16 = 34%) and other sites (8 = 17%). Radiation therapy consisted of 60 Gy (primary region, N+) or 50 Gy (N0) in daily fractions of 2 Gy each over six weeks. During week 1 and 5 of radiotherapy two courses of chemotherapy with 5-FU (600 mg/m2/day, i.v. continuous infusion for five days) and cis-platin (25 mg/m2/day i.v. bolus for five days) were administered. 43/47 patients (91%) responded to therapy. 34/47 (72%) patients achieved a complete remission, 9/47 (19%) a partial remission, and 4/47 (9%) no change. With a minimum follow-up of 26 months 17/47 patients (36%) are alive and NED, 4/47 (9%) are alive with tumour. 18 patients (38%) died of cancer, eight patients (17%) died of second tumours, intercurrent diseases and of unknown reasons. Actuarial four-year survival is 45% (stage III: 56%, stage IV: 42%), four-year NED survival is 35% (stage III: 68%, stage IV: 18%). There were no loco-regional recurrences after additional surgical treatment of the primary and the neck following complete remission. In contrast after RCT alone and complete remission local recurrences in 6/21 patients (29%) and regional recurrences in 5/24 patients (21%) occurred. We conclude that simultaneous RCT is a new very effective treatment modality of locally advanced head and neck tumours producing superior loco-regional control compared to conventional management.     

Zur Therapie von zervikalen Lymphknotenmetastasen ohne bekannten Primärtumor

Background

The primary tumor remains unknown in approximately 3 to 9% of patients with lymph node metastases in the neck. Management of these patients is still controversial particularly because of the commonly as poor assessed prognosis. The treatment outcome was surveyed by a retrospective analysis, trying to identify prognostic factors.

Patients and Method

From 1979 through 1993, 64 patients with metastatic carcinoma of unknown primary tumor involving neck lymph nodes were treated. Most of them (n=40) were squamous cell carcinomas. Forty-eight patients underwent surgical resection of the involved nodes by neck dissection or excisional biopsy. Surgery was performed in 41 patients before and in 7 patients after radiotherapy. Additional chemotherapy was administered to 12 patients (simultaneously to 11 patients). The irradiated volume included both sides of the neck, the supraclavicular region and the whole pharynx. The mean radiation dose was 59 Gy. In 32 patients, an additional boost to epipharynx (n=23) and/or large lymph nodes (n=11) was given (mean: 12 Gy) by external beam therapy, in 2 cases by interstitial implants (22 Gy). Mean follow-up time was 8 years (range: 7 months to 15 years, median: 9 years).

Results

Fifty-two out of 64 (81.2%) patients came into a complete remission and 12 into a partial remission. The cause specific survival after 5 years for the whole group was 51.0±7%, the overall survival 38,8±7%. Within the irradiated area the tumor control was (68.3±7%, the distant metastatic-free survival 70.0±7%. Best results showed patients after surgery + radiation (n=48) with 67% overall survival at 5 years versus 0% (median: 9.2 months) without surgery (n=16), and patients with lymph nodes located above the glottic level (n=49) 63.2% versus 9,0% (median: 1.2 years, n=12). The primary tumor appeared in 9 patients (4 times above the clavicles), once in the irradiated volume.

Conclusion

Patients with cervical metastases of unknown primaries do not fare worse than patients with advanced carcinoma of head and neck and should be treated with a curative intent preferably by surgery and radiotherapy.     

Interstitial Brachytherapy with Ir-192 Low-Dose-Rate in the Treatment of Primary and Recurrent Cancer the Oral Cavity and Oropharynx

AIM: To evaluate the impact of postoperative interstitial brachytherapy with and without external radiotherapy in the treatment of primary and recurrent squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Between 1985 and 1997, a total of 318 patients were treated by interstitial Ir-192 low-dose-rate brachytherapy as part of their primary (n = 236) or recurrent treatment (n = 82). There were 263 male (83%) and 55 (17%) female patients. The distribution of UICC (1997) stages was as follows: I (61 patients, 19%), II (71 patients, 22%), III (58 patients, 18%), IV (128 patients, 40%). The primary tumor site was located in the oral cavity in 201 patients (63%), in the oropharynx in 86 patients (27%), lower lip in 19 patients (6%) and other regions in twelve cases (4%). Treatment concepts did not vary over the time and were dictated by the initial tumor extension: a total of 175 patients (55%) received a combination of surgery, interstitial brachytherapy (23-25 Gy) and external radiotherapy (50-60 Gy), 60 patients (19%) surgery and interstitial brachytherapy (45-55 Gy) alone. Advanced disease not amenable to primary surgery was either treated by radiochemotherapy and interstitial brachytherapy in 39 patients (12%) or a combination of interstitial brachytherapy, external radiotherapy and interstitial hyperthermia in 44 patients (14%). RESULTS: Overall survival rates following primary and recurrent treatment were 50 +/- 4% and 29 +/- 5%, respectively, at 5 years (p < 0.0001). A significant impact on overall survival rate was noted for UICC stage: patients in stage I/II had survival rates of 64 +/- 5% and 57 +/- 10%, respectively, while patients in stage III/IV had survival rates of 39 +/- 5% and 15 +/- 5%, respectively, at 5 years (p < 0.0001). In addition, grading (p = 0.01) and hemoglobin levels (p = 0.05) had a significant influence on overall survival. Local tumor control rates for all patients were 74 +/- 3% and 57 +/- 7% at 5 years following primary and recurrent treatment (p = 0.01), respectively. The 145 patients treated for primary disease by a uniform concept of surgery, interstitial brachytherapy and external radiotherapy achieved excellent local control rates with 92 +/- 4% (stage I/II) and 65 +/- 6% (stage III/IV) at 5 years. Late treatment-related toxicity with soft tissue necrosis and/or osteonecrosis requiring mandibular resection was 7.5%. CONCLUSION: Local tumor excision followed by postoperative interstitial brachytherapy with and without external radiotherapy is associated with excellent locoregional control, a low risk of chronic sequelae and may therefore considered as a new approach avoiding mutilating radical surgery.     

Weichteilsarkome des Kopf-Hals-Bereichs beim Erwachsenen

Purpose

To analyse the experience treating soft tissue sarcomas of the head and neck at the Massachusetts General Hospital, Boston. Detailed results have been published previously [17].

Patients and Method

Between 1972 and 1993, 57 patients were treated curatively with radiation alone (n=13) or combined surgery and pre- and/or postoperative irradiation (n=44). Gross complete resection was achieved in 82% of patients and margins were negative in 5 patients. Doses ranged from 36.0 to 79.2 Gy (median 64.8 Gy), usually conventionally fractionated. In 16 patients protons were used. Median follow-up time was 4.3 years (range 1.1 to 16.8 years).

Results

After 5 years, patients with angiosarcomas (n=11) and patients with other tumor, types (n=46) had locoregional control rates of 24% and 69%, distant failure rates of 58% and 17%, and overall survival rates of 31% and 74%, respectively (p<0.01). In the group without angiosarcomas, prognostic factors were tumor grade (for overall survival) and T stage (for locoregional control) (p<0.05). Particularly, gross completely resected T1 tumors had a locoregional control rate of 91%. Patients with locoregional recurrence were at increased risk to die (p=0.004 in multivariate analysis). Patients with and without direct tumor extension to neurovascular structures, bones, organs, or skin had distant failure rates of 27% and 0%, respectively (p=0.031). In multivariate analysis, direct extension was additionally a negative prognosticator of overall survival (p=0.034).

Conclusion

1. Angiosarcomas of the head and neck have a considerably poorer prognosis than other soft tissue sarcomas of this region. 2. Head and neck sarcomas have a higher local recurrence rate than for example soft tissue sarcomas of the extremities. Optimisation of local treatment through combination of surgery and high-dose irradiation, however, can achieve improved results, especially for prognostically favourable subgroups. 3. In addition to tumor grade and size, direct tumor extension may be a useful additional staging parameter.     

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.     

Daytime pulsed dose rate brachytherapy as a new treatment option for previously irradiated patients with recurrent oesophageal cancer

The aim of this study was to evaluate the feasibility, effects, and toxicity of pulsed dose rate (PDR) brachytherapy for re-irradiation of oesophageal carcinoma. A total of 16 patients (median age 67 years) with inoperable recurrences from oesophageal cancer after primary radio-(chemo)-therapy (median 50 Gy) were re-irradiated using PDR brachytherapy ((192)Ir, 37 GBq). Treatment was carried out on an outpatient basis applying a weekly 5 Gy daytime schedule (0.5 Gy pulse(-1) h(-1), total dose 15-20 Gy). The dose was prescribed 10 mm from the mid-dwell position and encompassed the clipped tumour extension with 2 cm margins. The use of clips for delineation of tumour extent and catheter movement during irradiations was evaluated. All 61 PDR treatments were applied safely. The median catheter movement was 5 mm, range 2-12 mm. After a median follow-up of 8 months, three patients had a complete and five a partial remission. Body weight increased in 5 of 16 (31%) and was stable in 4 of 16 (25%) patients, respectively. The median grade 2 (RTOG/EORTC) dysphagia-free survival was 17 months. Seven patients experienced grade 1, five grade 2, and one grade 3 late toxicity. Three patients with uncontrolled locoregional disease showed grade 4 complications (oesophago-tracheal fistulae (n=2), fatal arterial bleeding (n=1). Daytime PDR brachytherapy proved to be feasible and provided effective palliation. Toxicity remains a major problem. Thus, total dose should be restricted to <15 Gy in this palliative situation.     

Outcomes of radiation therapy for maxillary sinus carcinoma

PURPOSE: We evaluated the outcome of radiation therapy for maxillary sinus carcinoma treated in our institution. MATERIALS AND METHODS: From 1984 to 2001, 48 patients with maxillary sinus carcinoma were irradiated with or without chemotherapy and surgery. Patients ranged from 20-89 years of age (median, 68 years) and included 29 men and 19 women. The clinical T factors for these patients, according to the UICC classification (1997), were T2(n = 2), T3(n = 13), and T4(n = 29). Lymph node involvement was observed in 13 patients. The follow-upperiod ranged from 2.5 to 150 months (median, 25 months). The total radiotherapy dose ranged from 40 Gy to 72.8 Gy. Forty-three patients underwent surgery. Intra-arterial chemotherapy was delivered in 39 patients, and systemic chemotherapy was delivered in 7 patients. Fourteen patients were classified as "unresected" (radiation therapy with or without antrostomy), and 34 patients as "resected" (partial, total, or extended total maxillectomy with pre- or postoperativeirradiation). RESULTS: The 5-year overall survival rate(OS), cause-specific survival rate(CSS), and local control rate(LC) of all patients were 52%, 64%, and 75%, respectively. There was no significant difference between the "uaresected" and "resected" groups in OS, CSS, or LC. Local recurrence was observed in 12 patients. In the "resected" group, for local control, it was important to reduce viable tumor before maxillectomy. Preoperative > or = 60 Gy irradiation was considered to be effective to reduce tumor viability. CONCLUSION: There was no significant difference between the "unresected" and "resected" groups in OS, CSS, or LC. In the "resected" group, preoperative irradiation > or = 60 Gy was considered to be effective for local control. In radical treatment of maxillary sinus carcinoma, maxillectomy is not always necessary. Concurrent chemoradiation therapy with or without antrostomy is a reasonable treatment strategy.