Comparison of dosimetry with magnetic resonance and computed tomography imaging delineation of surgical bed volume in breast cancer irradiation.

Background: Postoperative radiotherapy after conservative surgery for patients with breast cancer usually includes focal over-irradiation (boost) to the surgical bed (SB). Irradiation planning using computed tomography (CT) is difficult in many cases because of insufficient intrinsic soft tissue contrast. To ensure appropriate radiation to the tumor, large boost volumes are delineated, resulting in a higher dose to the normal tissue. Magnetic resonance imaging (MRI) provides superior soft tissue contrast than CT and can better differentiate between normal tissue and the SB. However, for SB delineation CT images alone remain the pathway followed in patients undergoing breast irradiation. This study aimed to evaluate the potential advantages in boost dosimetry by using MRI and CT as pre-treatment imaging. Methods: Eighteen boost volumes were drawn on CT and MRI and elastically co-registered using commercial image registration software. The radiotherapy treatment plan was optimized using the CT volumes as the baseline. The dose distributions of the target volumes on CT and MRI were compared using dose-volume histogram cutoff points. Results: The radiation volumes to the SB varied considerably between CT and MRI (conformity index between 0.24 and 0.67). The differences between the MRI and CT boost doses in terms of the volume receiving 98% of the prescribed dose (V98%) varied between 10% and 30%. Smaller differences in the V98% were observed when the boost volumes were delineated using MRI. Conclusion: Using MRI to delineate the volume of the SB may increase the accuracy of boost dosimetry.

Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

MOPP chemotherapy versus extended-field radiotherapy in the management of pathological stages I-IIA Hodgkin's disease.

In order to assess whether mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (CT), which is less expensive and more easily available than radiotherapy (RT), is at least as effective as RT in terms of cure rate and has less iatrogenic damage, 89 consecutive patients with Hodgkin's disease (HD) (pathological stage I-IIA) were randomly allocated to receive mantle plus lumbar bar RT (36-45 Gy) or CT (six courses of MOPP). Forty-five patients were entered in the RT group and 44 in the CT group. The median follow-up was 60 months. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 patients in the CT group. Overall survival (OS) and disease-free survival (DFS) were, respectively, 87.2% and 72.7% in the CT group and 93.5% and 74% in the RT group. Survival probability of relapsing patients was 76% for the patients in the RT group and 45% in the CT group. Treatment-related complications were more severe in the CT group as compared with the RT group.

Radiotherapy plus lonidamine in non-small cell lung cancer.

The current experience on combining lonidamine and radiation therapy in the treatment of non-small cell lung cancer was reviewed by the author. Six studies have been published on this subject: four were randomized trials comparing lonidamine plus radiotherapy versus radiotherapy alone. Total number of cases reported in these studies and length of follow up are still insufficient to draw a conclusion. The available data demonstrate, however, a significant improvement of time to progression in the group receiving radiotherapy plus lonidamine compared to the group receiving radiotherapy alone. No clear effect was observed on overall survival, which was only marginally superior in the group treated with lonidamine. Further studies are needed to confirm these data and to define the optimum dose schedule.

Sequential chemoradiation therapy with vinorelbine, ifosfamide, and cisplatin in stage IIIB non-small cell lung cancer: a phase II study.

Meta-analysis has demonstrated survival benefit for patients with stage IIIB non-small cell lung cancer treated with sequential chemoradiotherapy versus radiotherapy alone. The introduction of chemotherapy as part of a multimodality approach has improved the outcome in this poor prognostic subset of cancer patients. In the present phase II study we evaluated the safety and activity of a new cisplatin-based three-drug regimen consisting of vinorelbine/ifosfamide/cisplatin (VIP) followed by curative thoracic irradiation in 28 patients with stage IIIB non-small cell lung cancer. Patients received vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 g/m2 on day 1 (with mesna), and cisplatin 80 mg/m2 on day 1 every 3 weeks. After three courses of induction chemotherapy, patients with objective response or stable disease were eligible for thoracic radiotherapy. Twenty-six of the 28 patients received at least three courses of chemotherapy and were evaluable for response. The response rate to induction VIP was 58% (15 of 26 patients; one complete response and 14 partial responses). Seven patients had disease stabilization and four progressed during chemotherapy. Radiation treatment started from 4 to 6 weeks after the end of chemotherapy with standard fractionation (200 cGy/day, 5 fractions/wk/6 wk). Eighteen of 22 patients started thoracic irradiation; 14 completed the treatment plan, reaching the total dose of 60 Gy. The most relevant acute and late toxicities of radiotherapy were grade 3 dysphagia and pneumonitis in two patients and grade 3 lung fibrosis in six patients. By comparing the tumor volumes before and after radiation treatment we observed six clinical remissions, three stable diseases, and five local progressions. The first site of recurrence was local in 10 of 18 patients (56%), distant in seven patients (38.8%), and both local and distant in one patient. Median progression-free survival and overall survival for the patients treated with radiotherapy (18 patients) were 14 months (range, 4 to 36 months) and 26 months (range, 7 to 54+ months), respectively; the 1- and 2-year survival rates were 61% and 52%. Curative thoracic radiotherapy was well tolerated after VIP induction chemotherapy; it reduced residual tumor volume in six patients.

Profile of radiotherapy departments contributing to the Cooperative Group of Radiotherapy of the European Organization for Research and Treatment of Cancer.

PURPOSE: Since 1982, the Radiotherapy Group of the European Organization for Research and Treatment of Cancer (EORTC) is carrying out a Quality Assurance program that includes the evaluation of the structure and human resources of 50 centers actively participating in protocols of clinical research in radiotherapy. METHODS AND MATERIALS: One or two site visits were made by a team of radiation physicists and physicians. A detailed questionnaire was circulated to these radiotherapy centers to collect and update standardized figures on the status and activities of each center, to clarify some obscurities encountered during on-site visits, and to extend investigations to issues that were not addressed during local audits. RESULTS: This article reports on departmental infrastructure, staff and equipment workload, and quality control procedures carried out by single institutions. Large variations in equipment and staff are observed among participating centers. Comparisons between data collected in the early 1980s and during a recent update show no difference in workload per megavoltage equipment and per simulator. The number of cancer patients treated per year per radiotherapist seems to slightly diminish, especially in centers that experienced a considerable staff shortage a few years ago. The most significant improvement is observed for the number of cases treated per year per member of the radiation physics team. The radiographer's workload shows an opposite trend. CONCLUSIONS: Our database provides participating centers with strong comparative arguments to correct staff and equipment unbalances and to convince administrative authorities of priorities in decision making. The current analysis shows that the situation for equipment is unchanged in comparison with that observed 6 years ago. Efforts have to be put forth in some institutions to reduce the workload at simulators. A tentative profile and guidelines for minimum recommendations for European radiotherapy departments involved in clinical research are presented.

Results of a European randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas.

PURPOSE: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma. METHODS AND MATERIALS: A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m2, three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization. RESULTS: Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99). CONCLUSION: Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).

Role of portal imaging in clinical radiotherapy: Florence experience.

A portal imaging device developed at the Netherlands' Cancer Institute (NKI) in Amsterdam was provided to the Radiotherapy Section of the University of Florence as a partner of a cooperative study on quality assurance (QUIRT) granted by the EC (AIM Project). The device was used for portal imaging in 30 patients treated for tumors of different sites (5 rectum, 6 prostate, 5 Hodgkin's lymphomas, 5 head and neck tumors, 9 other sites). Portal images were obtained three times per week over the whole treatment period. An off-line quantitative analysis of discrepancies with respect to the simulation image was performed for the 5 rectum cases; a similar analysis was also done on the portal images of 4 rectal cases treated at the NKI in Amsterdam. The analysis proved capable of demonstrating the existence of some systematic errors in both centres and the different level of global accuracy between them. The on-line use of the device was also able to demonstrate some major errors of patient setup during the first session, which were immediately corrected.

Adjuvant postoperative radiotherapy in rectal cancer: 148 cases treated at Florence University with 8 years median follow-up.

BACKGROUND AND PURPOSE: To analyse the outcome, the treatment related side effects, the prognostic significance of clinical parameters in a group of patients with rectal cancer receiving postoperative radiotherapy after radical resection. MATERIALS AND METHODS: From 1980 to 1990 148 consecutive patients with rectal carcinoma stage B2-B3 or C1-C2-C3 were treated with postoperative radiotherapy after radical surgery. All patients received 50 Gy in 25 sessions in 5 weeks. In 42 a "flash' dose of 5 Gy was also given within 24 h before surgery. Median follow up was 8.1 years. RESULTS: At 5 years the overall survival was 54%, the determined (cancer specific) survival 61%, the local recurrence-free survival 88%. The influence of stage, histotype, distance from anal margin, type of surgery, number of involved nodes and flash dose were analysed. Overall and determined survival and distant metastasis rate were significantly influenced (P < 0.005) by the pathological stage. Patients with more than 3 involved nodes presented a significantly lower determined survival (P < 0.001) and a higher distant relapse rate (P < 0.005) than those with 3 or less involved nodes. A higher determined survival (P < 0.01) was also found in patients receiving the preoperative "flash'; this group was however unbalanced in respect to the relative number of cases with 3 or less involved nodes. The incidence of major side effects requiring surgery or hospitalization for medical treatment was 35% before 1985 and 12% thereafter. The systematic use of small bowel visualization during simulation and the discontinuation of the flash dose were the main modifications introduced in the second period. As a consequence of the small bowel visualization the size of lateral fields was slightly reduced and some patients were excluded from the treatment. CONCLUSIONS: Value of postoperative radiotherapy to decrease the incidence of local recurrence was confirmed in this retrospective study; the incidence of side effects was however considerable and did not support the addition of chemotherapy as advised by the NIH consensus meeting. Our policy was therefore moved to preoperative irradiation whose combination with chemotherapy was recently reported to be better tolerated and highly effective.

Waldeyer's ring (WR) involvement in Hodgkin's disease.

Of 750 patients with stage I, II or III Hodgkin's disease, admitted to the University and Hospital Radiotherapy Divisions, Florence, between 1960 and 1981, 28 (3.7%) had involvement of Waldeyer's ring (WR). In 25 patients there was associated involvement of upper cervical nodes. Other factors associated with WR involvement were age over 55 years, lymphocyte predominant histological sub-type, uninvolved mediastinum, and size of involved upper cervical nodes greater than that of involved lower cervical nodes. These factors help to define indications for prophylactic irradiation of WR.

Postoperative pelvic radiotherapy with or without elective irradiation of para-aortic nodes and liver in rectal cancer patients. A controlled clinical trial of the EORTC Radiotherapy Group.

OBJECTIVE: The purpose of this randomized multicenter study was to assess the impact on disease free and overall survival of low dose irradiation to para-aortic nodes and liver in patients with a locally advanced resected rectal cancer receiving a 50 Gy postoperative pelvic radiotherapy. PATIENTS AND METHODS: Main inclusion criteria were: a curative resection for a histologically proved carcinoma of the rectum, Gunderson-Sosin stages B2-B3, C1-C3, age <70 years. The patients were randomized between pelvic irradiation (Lim-XRT): 50 Gy in 25 fractions over 5 weeks and extended irradiation (Ext-XRT): same scheme/doses in the pelvis and extended fields on para-aortic nodes and liver, delivering 25 Gy in 19 fractions over 25 days. From 1983 to 1992, 484 patients were enrolled by 18 EORTC institutions and 29 patients were ineligible. The end-points were local and distant relapses, toxicity and survival. RESULTS: Compliance to treatment: 87.2% in Lim-XRT arm and 71.8% in Ext-XRT arm. Moderate acute hematological and hepatic toxicities were significantly increased in Ext-XRT arm. Among 325 patients at risk, 44 suffered a severe intestinal complication requiring surgery in 29. The 5- and 10-year estimates of disease free survival were respectively 42 and 31% in Lim-XRT arm and 47 and 31% in Ext-XRT arm (ns). The corresponding figures for overall survival were respectively 45 and 40% in Lim-XRT arm and 48 and 37% in Ext-arm (ns). The 10 years estimate of intra-pelvic failures was approximately 30% in both arms. Patients in Ext-arm appeared to have a slight shorter interval free of liver metastases (P=0.047). CONCLUSION: Low dose irradiation to the para-aortic nodes and liver did not improve survival for patients with resected adenocarcinoma of the rectum.

The volume effect in radiation-related late small bowel complications: results of a clinical study of the EORTC Radiotherapy Cooperative Group in patients treated for rectal carcinoma.

PURPOSE: The purpose of this study was to quantify the correlation between irradiated small bowel volume and late occurring small bowel complications. METHODS: Small bowel volumes in the high-dose region were measured using orthogonal barium films for 203 patients treated for rectal carcinoma with pelvic postoperative radiotherapy to 50 Gy in an EORTC multicentric study. RESULTS: The 5-year estimate of late pelvic small bowel obstruction requiring surgery was 11%. No correlation between the irradiated small bowel volume and obstruction was detected. The actuarial 5-year estimate of chronic diarrhea varied from 31% in patients with irradiated small bowel volumes below 77 cm3 to 42% in patients with volumes over 328 cm3. This correlation was significant in the univariate and multivariate analysis (p = 0.025). The type of rectal surgery significantly influenced the incidence of chronic diarrhea and malabsorption, the actuarial 5-year estimate being 49% and 26% after low anterior resection and abdominoperineal resection, respectively (p = 0.04). CONCLUSIONS: This study demonstrated that there is a volume-effect in radiation-induced diarrhea at a dose of 50 Gy in 25 fractions. No volume-effect for small bowel obstruction was detected at this dose-level in pelvic postoperative radiotherapy. A review of the literature data on small bowel obstruction indicates that the volume effect at this dose level can only be demonstrated in patients who were treated with extended field radiotherapy (estimated small bowel volume 800 cm3) after intra-abdominal surgery.

Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study.

BACKGROUND: Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy. PATIENTS AND METHODS: From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment. RESULTS: There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05). CONCLUSION: The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.

Asynchronous bilateral non-Hodgkin's lymphoma of the testis: report of three cases.

Asynchronous involvement of both testes by non-Hodgkin's lymphoma was observed in 3 patients ranging in age from 38 to 82 years. According to the Working Formulation, all cases were classified as large cell immunoblastic lymphomas, and immunohistochemical studies demonstrated a T-cell phenotype in 1 patient and a B-cell phenotype in 2 patients. Relapse to the contralateral testis occurred after a mean interval of 6 months. The negative prognostic impact of these neoplasms is confirmed in the present series, since 2 patients died of disease 7 and 9 months after diagnosis and 1 patient had a laterocervical and Waldeyer's ring recurrence after 1 year.

Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment of advanced cervical cancer.

The role of chemotherapy in the management of advanced cervical cancer has been long debated. Whereas some phase II trials have shown promising results with neoadjuvant chemotherapy followed by irradiation, most phase III trials failed to demonstrate any benefit with this sequential treatment in terms of loco-regional control and survival, mainly because chemotherapy could cause accelerated tumor clonogen resistant cell repopulation The data on cisplatin-based neoadjuvant chemotherapy before surgery appear to be more promising. This treatment modality can increase the operability rate and reduce the incidence of positive nodes and other pathological risk factors. However, very few randomized trials comparing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy versus conventional irradiation treatment are currently available, whilst data about long-term survival of chemo-surgical-treated patients are scanty. Recently five prospective randomized trials compared concurrent cisplatin-based chemotherapy and irradiation versus hydroxyurea plus irradiation or irradiation alone. All showed a significant improvement in the outcome of patients treated with concurrent cisplatin-based chemoradiation. Based on these data, the National Cancer Institute released a Clinical Announcement stating that concurrent cisplatin-based chemoradiation should be the new standard of therapy for high-risk early stage and locally advanced cervical cancer. The introduction of taxanes in both neoadjuvant chemotherapy followed by radical hysterectomy and concurrent chemoradiation could further improve the results of these two treatment modalities. A multicenter randomized trial comparing chemo-surgical treatment with concurrent chemoradiation is warranted to better define the optimum therapeutic strategy for patients with advanced cervical cancer.

Quantitative magnetic resonance imaging in cervical carcinoma: a report on 30 cases.

T1 and T2 relaxation times were calculated, before radiation therapy, in 30 patients with cervical carcinoma. Eight healthy young women were submitted to magnetic resonance imaging (MRI) to determine T1 and T2 times of the normal cervix. Magnetic resonance imaging was repeated, in 22 patients, during radiation therapy and at follow-up. During treatment and follow-up, patients with complete tumour response showed a significant T1 reduction compared with the pre-treatment values. With persistence of palpable or visible tumour, T1 times showed a small decrease during therapy, and a marked increase at subsequent examinations. The results suggest that the modifications of T1 times, during radiation therapy and follow-up, could be considered as a useful discriminant between patients with differing tumour response.

Mediastinal involvement in Hodgkin's disease: prognostic factors and distribution of intrathoracic adenopathies.

The files and the roentgenographic documentation of 624 patients affected by Hodgkin's disease have been reviewed. The presence and location of involved nodes in the different lymph node chains of the mediastinum have been determined and correlated with the distribution of the main anatomoclinic prognostic parameters of the disease. Feminine sex, histology of nodular sclerosis, presence of constitutional symptoms and age younger than 36 were found to be significantly more frequent in patients with mediastinal adenopathies than in patients with a normal mediastinum. Patients with mediastinal adenopathy at presentation were also more likely develop pulmonary involvement as first evidence of new manifestation of disease after the primary treatment. A different probability to be affected by disease was evident among the different lymph node groups in the mediastinum. The involvement of hilar nodes appeared to accompany a more advanced stage of disease and to favour the adjacent lung extension.

Cost-effectiveness of chest X-ray follow-up of patients treated for seminoma of the testis.

The authors report on a consecutive series of 253 cases of seminoma of the testis followed with periodic chest X-ray examinations from a minimum of three to a maximum of 27 years. The detection rate of asymptomatic intrathoracic metastases (ITM) was considered together with the costs of the follow-up procedure. Chest X-ray follow-up is not advisable beyond one year from primary treatment, since most (14 of 18) ITM occur in the first year, the detection rate of ITM beyond this date is too low (0.11% patients/year), and the related costs are too high (over $130,000 per ITM detected). Chest X-ray follow-up is questionable even in the first year after primary treatment for Stage I cases because of the low detection rate (1.38% patients/year) and the high costs (over $14,000 per ITM detected), whereas it appears to be opportune in Stages IIA and IIB.

Hodgkin's disease associated with sarcoidosis: case report.

Coexistence of true systemic sarcoidosis and Hodgkin's disease has been reported as a very exceptional occurrence. In this paper a case observed at the Institute of Radiology of Florence is described of which the most interesting features were 1) sarcoidosis appeared 5 years earlier than Hodgkin's disease; 2) at staging lymphography the paraortic nodes appeared extensively enlarged and showed multiple filling defects; 3) at laparotomy the nodes removed were histologically affected by sarcoidosis only; 4) multiple foci of sarcoidosis were found also in the spleen and liver; 5) this feature led us to refrain from irradiating the abdomen; 6) one year later a further enlargement of paraortic nodes was observed; 7) a second laparotomy revealed Hodgkin's infiltration in the removed nodes; 8) irradiation of the inverted "y" field was followed by complete regression of the nodes and the patient is alive and well 2.5 years after the relapse.

Salvage with radiotherapy of postsurgical relapses of endometrial cancer.

From January 1960 to June 1974, 71 patients with a postsurgical relapse of endometrial adenocarcinoma have been referred to the Radiology Institute of the University of Florence. Eleven patients showed hematogenous metastases; the remaining 60 cases showed locoregional relapses and were treated with radiotherapy. Forty-eight patients, whose relapse was localized to the pelvis, vagina, inguinal nodes or perineal scar, were treated with a radical aim (4,500-6,000 rad in 5-6 weeks); the treatment was palliative in 12 cases with abdominal extrapelvic relapse. The therapeutic response was not evaluated in 8 patients lost to follow-up shortly after the treatment. In the cases treated with a radical scope, a complete regression was attained in 22 of 43 (51%); a survival rate of 16 of 43 (37%) was attained at 5 years. In 9 cases treated with a palliative aim, only subjective remission was attained, and no patient was alive one year after the therapy. The most favorable therapeutic response was attained in the vaginal relapses (50% survivors at 5 years) and the cases with a late recurrence (more than 3 years) after the initial surgery. No definite correlation was found between the prognosis of the relapse and the histological grading of the primary tumor.