Purpose: The optimal therapy for locally advanced malignant thymoma is controversial. We review our experience with a multimodal approach in 63 consecutive cases.
Patients and methods: Forty-three ...patients had stage III and 20 stage IVa disease. Surgery with radical intent was initially performed in 30 cases, while 33 cases not amenable to radical surgery underwent neoadjuvant treatment (radiotherapy in 8 and chemotherapy in 25) before surgical reassessment. All patients, whether or not surgically resected, received radiation therapy.
Results: Radical resection (RR) was performed in 20 patients ab initio (all stage III) and in 12 patients after neoadjuvant treatment (eight stage III and four stage IVa). With the addition of patients radically operated with neoadjuvant treatment, the radical resection rate increased from 46 to 65% in stage III patients, and from 0 to 20% in those with stage IVa disease, respectively. Radical surgery was associated with longer progression free survival and overall survival according to both univariate analysis (
P<0.001 and 0.01, respectively) and multivariate analysis after adjustment for age, gender, histology and disease stage (
P<0.001 and <0.02, respectively). Progression free survival (median 56.9 months) was slightly lower in patients undergoing radical surgery after neoadjuvant approaches than in those radically resected ab initio (median not achieved), but overall survival (median not achieved) was similar in both groups. Subtotal surgical resection promoted complete response to subsequent radiation therapy. This condition significantly correlated with a better outcome.
Conclusions: Complete surgical resection is an independent prognostic parameter in locally advanced thymoma treated with a multimodal approach. Preoperative treatment to increase the complete resection rate could improve the overall survival of these patients.
The objective of this study was to assess the utility of CT-MRI image fusion software and compare both prostate volume and localization with CT and MRI studies. We evaluated the differences in ...clinical volumes in patients undergoing three-dimensional conformal radiation therapy for localized prostate cancer. After several tests performed to ensure the quality of image fusion software, eight patients suffering from prostate adenocarcinoma were submitted to CT and MRI studies in the treatment position within an immobilization device before the start of radiotherapy. The clinical target volume (CTV) (prostate plus seminal vesicles) was delineated on CT and MRI studies and image fusion was obtained from the superimposition of anatomical fiducial markers. A comparison of dose-volume histograms relative to CTV, rectum, bladder and femoral heads was performed for both studies. Image fusion showed a mean overestimation of CTV of 34% with CT compared with MRI. Along the anterior-posterior and superior-inferior direction, CTV was a mean 5 mm larger with CT study compared with MRI. The dose-volume histograms resulting from CT and MRI comparison showed that it is possible to spare a mean 10% of rectal volume and approximately 5% of bladder and femoral heads, respectively. This study confirmed an overestimation of CTV with CT images compared with MRI. Because this finding only allows a minimal sparing of organs at risk, considering the organ motion during each radiotherapy session and the excellent outcomes of prostate cancer treatment with CT based target identification, we are still reluctant to reduce the CTV to that identified by MRI.
Background: Surgery is the primary treatment for patients with stage I, II, or IIIA non–small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely ...unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established. Methods: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m2 on day 1), vindesine (3 mg/m2 on days 1 and 8), and cisplatin (100 mg/m2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided. Results: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P = .589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P = .128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival. Conclusion: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.
The optimal timing and sequencing of adjuvant radiotherapy and chemotherapy after breast-conserving surgery for early invasive breast cancer is controversial. Several studies demonstrated that ...postoperative radiation therapy significantly reduces the incidence of breast recurrences. For patients who do not need systemic treatment, the interval between surgery and the start of radiotherapy should not exceed eight weeks. For node-positive and high-risk patients receiving breast-conserving treatment, adjuvant chemotherapy should be administered prior to radiotherapy, but the delay of radiation should not exceed 20–24 weeks.
Side effects and complications of radiotherapy can be expected to increase when chemotherapy is administered concurrently. In particular, antracycline-based chemotherapy regimens increase the damage to heart muscle and coronary arteries: to avoid the risk of ischemic cardiovascular disease, radiotherapy must be performed after the end of systemic treatment.
Department of Hematology, Ospedale SS. Antonio e Biagio, Alessandria, Italy.
BACKGROUND: Hodgkin's disease (HD) after the age of 65 years is uncommon and there are no published data on chemotherapy ...regimens devised for elderly HD patients. PATIENTS AND METHODS: From 1990 to 1993, 25 elderly HD patients were treated with the CVP/CEB regimen: chlorambucil 6 mg/sqm p.o. days 1 through 7, vinblastine 6 mg/sqm i.v. on day 1, procarbazine 100 mg/sqm p.o. days 1 through 7, prednisone 30 mg/sqm p.o. days 1 through 7, cyclophosphamide 500 mg./sqm i.v. day 15, etoposide 70 mg/sqm i.v. day 15, bleomycin 10 mg/sqm i.v. day 15. Each course was repeated every 4 weeks. Stage I and II patients were treated with 3 courses followed by involved field radiotherapy, while more advanced stage patients received 6 courses and radiotherapy was limited to bulky areas. The results of the CVP/CEB regimen are retrospectively compared to those of 74 elderly patients treated between 1982 and 1989 and subdivided into the following 2 groups: 32 patients treated according to the same therapy used at that time in younger patients, and 42 patients given alternative low aggressivity or palliative treatment. RESULTS: CVP/CEB is a well-tolerated regimen, with only 1 (4%) toxic death and 2 (8%) protocol violations/interruptions. The CVP/CEB complete remission rate (73%) compares favorably with our previous groups of patients, mainly because of the lower toxic death rate. However, the CVP/CEB relapse-free survival rate is lower than that of patients treated with more aggressive conventional regimens (47% vs. 77%, p
Elderly Hodgkin's disease patients have a poor prognosis. The question arises whether these patients need aggressive treatment or a palliative strategy. So far, as a consequence of the scarcity of ...trials designed for them, useful information can be obtained only by retrospective analyses.
We retrospectively studied clinical data from 567 patients recorded from 1982 to 1989 in the Piemonte Hodgkin's Disease Register (PHDR). The 65 patients over 65 years of age were compared to younger ones. We analyzed the role of disease independently of confounding variables, mainly inadequacy of staging and/or treatment, comorbidity and toxicity.
In the elderly comorbidity was as high as 35%. Forty elderly patients (60%) entered a suboptimal plan with a low degree of aggressivity, which was different from the usual PHDR protocol. Elderly patients also had a high proportion of subsequent protocol interruptions (25%). Chemotherapy dose intensity was negatively affected by advanced age (p < 0.01 after both 3 and 6 courses of chemotherapy). Toxic deaths were significantly higher in elderly patients than in younger ones (14% vs 1%; p < 0.05). CR rates, overall survival (OS), disease-specific survival (DSS) and event free survival (EFS) were all significantly influenced by age (p < 0.01). Relapse-free survival (RFS) in patients achieving CR did not differ according to age class (77% vs 60%; p = ns). RFS was better in elderly patients entering the PHDR protocols than in those following an alternative plan (75% vs 54%; p = 0.04); however, elderly patients treated according to PHDR guidelines showed a higher incidence of toxic deaths than those treated less aggressively (23% vs 8%). The two groups had similar EFS (36% vs 24%; p = ns).
Elderly patients who achieve CR can have good RFS and cure is possible, but the toxic cost of conventional strategies is unacceptable and selected strategies still must be found.
Between 1974 and 1988, 21 patients with intrathoracic recurrences of thymoma received radiotherapy with radical intent; surgery was always attempted when considered feasible: 11 patients were ...partially (6 cases) or totally (5 cases) resected before irradiation, while in the other 10 radiotherapy was the only treatment. In 7 cases the recurrence was confined to the anterior mediastinum, 9 had pleural nodules without mediastinal lesions and 5 had both mediastinal and pleural lesions. Mediastinal recurrences were treated by opposed parallel mediastinal fields with 2/3 of the dose delivered through the anterior port: doses ranged between 38 and 44 Gy; a boost of 10-16 Gy was given in patients not radically resected. Pleural nodules were treated with a variety of techniques according to the extent of the lesions. The 7-year survival of the whole group was 70%; 5 patients died: 4 with intrathoracic progression and one with distant metastases. The survival was 74% in the 11 patients having received surgery, either radical or subtotal, and 65% in the 10 patients treated with radiotherapy alone: the difference is not significant. Patients with Karnofsky index greater than 70 had a significantly better survival (100%, versus 28%, p = 0.0015). This is a selected series of patients presenting recurrences still amenable to a radical treatment either by surgery and radiotherapy or by radiotherapy alone: the results confirm that an aggressive approach is warranted in patients in good general conditions with recurrences confined to the mediastinum and/or 1 hemithorax.
INTRODUCTION. The screening programmes are very challenging from the ethical perspective, and their impact in terms of morbidity and mortality make secondary colorectal cancer prevention a valuable ...public health intervention.
The target population people aged 50-69 years receive an invitation card with a test-tube for the fecal occult blood test (FOBT) and an immunochemical test is used for fecal occult blood. Subjects positive to FOBT are invited to perform a gastroenterologic examination and a full colonoscopy.
In the firt round of screening, 100% of the target population has been invited with an adhesion rate of 41.3%. A total of 1739 FOBT-positive subjects have been invited to the second level of the screening. 1429 of them have performed the gastroenterologic examination (83.9%). To date 956 full colonoscopies have been completed and the rate of subjects affected by carcinoma, malignant polyp and advanced adenoma has been equal to 23.5%.
Thanks to the reminders already sent, an increasing compliance has been registered with an increased rate of subjects with a low schooling that have performed a FOBT test. With the aim to optimize all the operative aspects of the screening programme it is already ongoing a set of meetings between health workers of Local Health Unit 4 and General Practioners.
In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by ...external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable.
Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients.
At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy.
For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.
Localized hyperthermia alone has been used for the treatment of cancer recurrences in which previous conventional therapies have failed. Since 1983 and 1988, 57 patients with 60 lesions have been ...heated by means of a microwave and radiofrequency system. Treatment protocol provided 45 minutes of heating at the intratumor temperature of at least 42°C, twice a week, for a total number of six, eight, or ten heating sessions. Invasive intratumor thermometry was performed for all lesions. Complete response (CR) was obtained in ten cases (16.6%) and partial response (PR) in 14 (23.4%). Higher rates of CR were observed in the chest wall (38.5%) compared with the head and neck area (11.4%), trunk (10%), and limbs (none). Adenocarcinoma was the most responsive histologic type (40%). Squamous cells carcinoma had 7.7% CR. the only case of undifferentiated carcinoma showed CR; there were none on five sarcomas. Long‐term local control (24 months) was approximately 7%. the multivariate analysis showed the statistical significance of the histologic variety (adenocarcinoma versus others, P < 0.0001). Side effects and complications of the treatment were minimal.
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