Giovanni Franchin

RADIOTHERAPY VERSUS RADIOTHERAPY ENHANCED BY CISPLATIN IN STAGE III NON-SMALL CELL LUNG CANCER

Abstract Between January 1987 and June 1991, 173 patients with inoperable non-small cell lung cancer, Stage III, were entered into a randomized trial comparing radiotherapy only (RT) (45 Gy/15 fractions/3 weeks) (arm A) versus RT and a daily low dose of cDDP (6 mg/m 2 ) (arm B). An overall response rate of 58.9% was observed in arm A and 50.6% in arm B, respectively. No differences in the pattern of relapse were noted between the two treatment groups. Median time to progression was 10.6 months for arm A and 14.2 months for arm B. Median survivals were 10.3 months and 9.97 months, respectively. Toxicity was acceptable and no treatment-related death occurred in either treatment schedule. In this study no significant advantage of the combined treatment over radiation therapy only was found. The encouraging results achieved in some trials together with the intractability of the disease suggest that further efforts should be made to optimize clinical trial protocols, perhaps by reviewing the radiobiological and pharmacological basis of the combined treatment.

Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy--a multicenter randomized trial.

PURPOSE To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx. METHODS AND MATERIALS Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week). RESULTS No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms. CONCLUSIONS The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity.

Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced epidermoid bronchogenic carcinoma. A randomized study

Between June 1980 and December 1983, 111 patients with inoperable epidermoid bronchogenic carcinoma (limited disease) were entered into a randomized trial comparing radiotherapy alone versus radiotherapy and combination chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), methotrexate, and procarbazine. Thirty‐five of 62 (56.4%) patients treated with 4500 rad in 15 fractions in 3 weeks and 19 of 49 (38.8%) patients treated with the same radiation treatment and chemotherapy had an objective response. The difference in response rate was not significant (P = 0.900). Median time to progression was 5.9 and 7.02 months, respectively, for the radiation treatment and the combined treatment. Median survival was 11.74 and 10.03 months, respectively, without statistically significant differences between the two groups of patients. The toxicity was acceptable and no treatment‐related death occurred in either treatment schedule. In this study no significant superiority of combined radiotherapy and chemotherapy treatment over radiation therapy alone was evidenced. Whether different chemotherapy regimens may prove more effective in this context should be clarified by further studies.

Radiotherapy for patients with early-stage glottic carcinoma : univariate and multivariate analyses in a group of consecutive, unselected patients

Radiotherapy (RT) has a remarkable success rate in the treatment of patients with glottic carcinoma. The objectives of the current study were to assess the results in a group of consecutive patients with comparable characteristics who were treated with RT (6‐megavolt photon linear accelerator) and to determine the prognostic factors that may influence local control in patients with early‐stage glottic carcinoma. The impact on local control of tobacco smoking and second primary malignancies also was investigated.

Detection and Restaging of Residual and/or Recurrent Nasopharyngeal Carcinoma after Chemotherapy and Radiation Therapy: Comparison of MR Imaging and FDG PET/CT

PURPOSE To compare the accuracy of magnetic resonance (MR) imaging and combined fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), alone and in combination, in detection and restaging treated nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS This retrospective study was performed after institutional review board approval and informed consent were obtained. Sixty-three consecutive patients treated for NPC underwent follow-up with both MR imaging and FDG PET/CT. Findings were evaluated according to the TNM classification. Final diagnosis was confirmed at biopsy or imaging follow-up for at least 6 months. Proportions and their 95% confidence intervals were computed; for comparison of data obtained separately from MR imaging and FDG PET/CT and those obtained from their combined use, the McNemar test was used. P < .05 was considered to indicate a statistically significant difference. RESULTS There was a trend toward greater overall accuracy of MR over PET/CT in detecting residual and/or recurrent NPC at the primary site; 92.1% (58 of 63 patients) for MR versus 85.7% (54 of 63) for FDG PET/CT (P = .16). Overall accuracy for tumor restaging was 74.6% (47 of 63) for MR and 73.0% (46 of 63) for FDG PET/CT (either modality used alone), but the overall combined accuracy was 92.1% (58 of 63) (all P values < .01). CONCLUSION MR imaging demonstrated a trend toward higher accuracy than did FDG PET/CT in detecting residual and/or recurrent NPC at the primary tumor site. The combined use of MR and FDG PET/CT was more accurate for tumor restaging than when either modality was used independently.

Tobacco smoking, alcohol drinking, and the risk of different histological types of nasopharyngeal cancer in a low-risk population

Nasopharyngeal carcinoma (NPC) is rare in western Countries. Tobacco smoking is a well-recognised risk factor, whereas the role of alcohol drinking is still in debate. We conducted a hospital-based case-control study in Italy on 150, histologically-confirmed, NPC cases of Caucasian ethnicity, aged 18-76years, including 118 undifferentiated NPCs and 22 differentiated squamous-cell NPC. Controls were 450 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Cases and controls were matched according to sex, age, and place of residence. Logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) while adjusting for known confounders. No significant association emerged between tobacco smoking and all NPCs (OR for current vs. never smokers=1.52; 95% CI: 0.89-2.60). Conversely, for differentiated NPC only, statistically significant elevated OR were associated with increasing smoking intensity (OR for ⩾15cigarettes/day=5.40; 95% CI: 1.34-21.76) and duration of the habit (OR for ⩾32years=4.48; 95% CI: 1.11-18.04). Although alcohol drinking was not, per se, significantly associated to NPC risk, the combination of tobacco smoking and alcohol drinking accounted for 57% of differentiated NPCs, whereas it accounted for only 14% of undifferentiated carcinomas. Our findings suggest that, in western populations, NPC includes two separate entities: the differentiated NPC, associated with tobacco smoking like other cancers of head and neck, and the undifferentiated NPC, upon which tobacco smoking has little or no influence.

Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up

PURPOSE We have previously shown the feasibility of delivering high doses of radiotherapy in malignant pleural mesothelioma (MPM) patients who underwent radical pleurectomy/decortication (P/D) or surgical biopsy. In this report, we present the long-term results of MPM patients treated with radical P/D followed by high doses of radiotherapy. METHODS AND MATERIALS Twenty consecutive MPM patients were enrolled in this prospective study and underwent radical P/D followed by high dose radiotherapy. The clinical target volume was defined as the entire hemithorax excluding the intact lung. The dose prescribed was 50 Gy in 25 fractions. Any FDG-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Nineteen patients received cisplatin/pemetrexed chemotherapy. Kaplan-Meier analysis was used to calculate rates of overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC). RESULTS The median follow-up was of 27 months. The median OS and PFS were 33 and 29 months, respectively. The median LRC was not reached. The Kaplan-Meier estimates of OS at 2 and 3 years were 70% and 49%, respectively. The estimates of PFS at 2 and 3 years were 65% and 46%, respectively. The estimates of LRC at 2 and 3 years were 68% and 59%, respectively. The predominant pattern of failure was distant: 7 patients developed distant metastases as the first site of relapse, whereas only 3 patients experienced an isolated loco-regional recurrence. No fatal toxicity was reported. Five Grades 2-3 pneumonitis were documented. CONCLUSIONS High dose radiation therapy following radical P/D led to excellent loco-regional control and survival results in MPM patients. A median OS of 33 months and a 3-year OS rate of 49% are among the best observed in recent studies, supporting the idea that this approach represents a concrete therapeutic option for malignant pleural mesothelioma.

Radiation treatment of glottic squamous cell carcinoma, stage I and II: Analysis of factors affecting prognosis

PURPOSE At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. METHODS AND MATERIALS Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. RESULTS Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. CONCLUSIONS According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.

The effect of granulocyte colony-stimulating factor on oral mucositis in head and neck cancer patients treated with hyperfractionated radiotherapy.

We investigated the effect of granulocyte colony-stimulating factor (G-CSF) administration on radiotherapy (RT)-induced oral mucositis in 26 consecutive patients with head and neck neoplasms, stages III and IV, treated with hyperfractionated RT. The first 13 patients were treated with RT alone and the remainder with RT + G-CSF. The two groups of patients were similar in age, sex, PS, primary site, stage, RT schedule and RT volume. Daily mucositis, median mucositis score, day of highest mucositis, requirement of parenteral nutrition, weight loss, treatment break, number of days of RT interruption were analyzed during RT treatment. No statistically significant differences were found between the two groups except for the number of patients who interrupted the treatment: 9/13 patients (69%) in the RT alone group versus 3/13 (23%) in the RT + G-CSF group (p < 0.05). Our observations indicate that G-CSF did not appear to have influenced the objective mucositis although it reduced the number of treatment breaks. In consideration of the cost of G-CSF, its prophylactic administration should be reserved only for patients at high risk of RT interruption.

The efficacy of radiotherapy in the treatment of intraocular metastases

From January 1980 to May 1991, 28 patients with intraocular metastases were seen at our Institute. Three presented with bilateral metastases and two developed contralateral involvement. Out of the 33 ocular metastases 27 were managed by radiotherapy. The most common primary tumour sites were breast (18/28 patients) and lung (3/28). 22 patients were treated with an 8 MV linear accelerator, using a 4 x 4 cm anterior direct field. The median dose was 40 Gy/20 fractions (range 28 Gy/14 fractions to 50 Gy/25 fractions). Of the 27 treatments reported, 16 resulted in a complete response (59%), six in a partial response (22%) and five resulted in no change (19%). Complete and partial responses lasted for a median time of 13 months (range of 3-89+ months). The median survival time from the start of ocular treatment was 13 months. The aim of radiation treatment is either to prevent or to postpone the visual loss caused by intraocular metastases.