Pierre Aletti

Conservative treatment by irradiation of epidermoid cancers of the anal canal: Prognostic factors of tumoral control and complications

UNLABELLED We analyzed in a retrospective series of patients treated by conservative irradiation for an epidermoid cancer of the anal canal (ECAC) the prognostic factors of locoregional control (LRC), survival, late severe complications (LSC), and sphincter conservation (SC). METHODS AND MATERIALS From 1976 until 1994, 118 patients presenting with an ECAC were conservatively treated (mean age, 65 years). According to the 1987 International Union Against Cancer (TNM) classification, they were: 19 T1, 70 T2, 22 T3, 7 T4, 94 N0, and 24 N1-3. The treatment started with external beam irradiation (EBI) (36 Gy in 3 weeks or 45 Gy in 5 weeks). Concomitant chemotherapy (5-fluorouracil and mitomycin C) was delivered to 31 patients. Two months later, a boost of 20 Gy was delivered by interstitial 192Ir brachytherapy to 101 patients and EBI in 5. Twelve other patients had an abdominoperineal resection (APR). The mean follow-up was 6 years. RESULTS At 5 years the overall survival was 60%, and specific survival (SS) was 75%; it was 94% for T1, 79% for T2, 53% for T3, and 19% for T4. In multivariate analysis, tumor size (> or = 4 cm), node involvement, and no response to the EBI were factors of poor prognosis for SS. Thirty-two locoregional recurrences occurred of which 21 were local recurrences in the 106 patients treated by a conservative schedule. Only tumor size and response to the EBI were prognostic factors on multivariate analysis for local and LRC. A total of 17 patients presented with LSC (Grade 3, 16 patients; and Grade 4, 1 patient), which was treated by APR in 4 patients and colostomy in 11 (of which 7 were definitive). The only significant prognostic factor for LSC in the multivariate analysis was the total extrapolated response dose of irradiation. The definitive rate of SC after conservative treatment in cured patients was 100% for T1, 82% for T2, 58% for T3, and 100% for T4. Since 1989, improvements of the technique have allowed reduction of the LSC in maintaining the same local control. CONCLUSION The results of this series are similar to those of the literature. The confirmation of pretherapeutic prognostic factors related to response to the treatment should allow us to adapt the therapeutic intensity for each case to obtain better tumor control, with as few sequelae as possible, to yield a better rate of SC.

Dose escalation with 3D-CRT in prostate cancer: French study of dose escalation with conformal 3D radiotherapy in prostate cancer—preliminary results

PURPOSE To evaluate the feasibility of dose escalation in a multi-institutional study in prostate cancer patients. METHODS AND MATERIALS Between October 1995 and October 1998, 164 patients with localized adenocarcinoma of the prostate were treated with 3-dimensional conformal radiotherapy at one of five French institutions. The dose of radiation was escalated from 66 to 80 Gy (ICRU point). The maximum dose to the rectal wall was limited to 75 Gy. RESULTS Results were compared in two groups, one (group 1) receiving the standard dose (n = 46 patients; 66 to 70 Gy) and the other (group 2) receiving the escalated dose (n = 118 patients; 74 to 80 Gy). There was no difference in the characteristics of patients between the two groups. The mean follow-up time was 32 months in group 1 and 17.5 months in group 2. No statistical difference between the two groups was observed in the incidence of late gastrointestinal and urinary toxicities. The probability of achieving a posttreatment prostate-specific antigen nadir of </=1 ng/mL in the 120 patients who did not receive neoadjuvant androgen-deprivation therapy was significantly higher in the dose-escalation group and was directly related to the dose of radiation given. CONCLUSION This multi-institutional study demonstrated the feasibility of escalating the dose of radiation to 80 Gy in prostate cancer patients.

Detection of errors in individual patients in radiotherapy by systematic in vivo dosimetry

Abstract We report 5 years of systematic measurements of the dose delivered to each patient undergoing radiotherapy treatment with photon beams in order to detect any systematic error that may have escaped the different checks performed at each step of planning and calculation prior to the first treatment session, or may have arisen during the set-up or the treatment delivery. For each patient the target-absorbed dose is derived from the entrance and exit doses measured by silicon diodes, on the beam axis at the patients skin. Depending on the discrepancies observed between the measured and expected doses we have set decision levels for the corrective actions to be taken. In addition these measurements allow us to obtain information on the overall accuracy or on the quality of a specific treatment. During 5 years, 7519 patients have been measured and 79 errors were detected. Half could have induced a variation of over 10% in the dose delivered. Seventy-eight out of 79 errors were of human origin. As part of an overall quality assurance programme, it is of the utmost importance to check the dose delivered for each patient undergoing radiotherapy treatment in order to avoid systematic underdosing or overdosing.

The study of tumoral, radiobiological, and general health factors that influence results and complications in a series of 448 oral tongue carcinomas treated exclusively by irradiation

PURPOSE Our aim was to study the different factors that influence the results and complications in a series of 448 carcinomas of the oral tongue treated from January 31, 1972 to December 31, 1986, by brachytherapy (Br) +/- neck dissection (181 cases) or combination of external beam irradiation and brachytherapy (EBI + Br) (267 cases). METHODS AND MATERIALS The patients distribution (TNM classification 1979) was: 125 T1, 186 T2, 128 T3, 9 T4Tx, 78% N0, and 22% N+. We used guide gutter or plastic tubes technique (Paris system dosimetry). Results at 5 and 10 years are: local control 68% and 64%, locoregional control 58% and 53%, specific survival 45% and 39%, and overall survival 44% and 27%. RESULTS In the univariate analysis for local control (LC) and overall survival (OS), we considered the tumoral factors. At 5 years, the LC for T1, T2, T3 are 93%, 65%, and 49%, and the OS 69%, 41%, and 25%, respectively (p < 0.002). The lesions of the undersurface of the tongue have a better LC (77%) than other localizations (64%) (p = 0.02). For general factors, the index of general health condition, age, and sex were not significant for LC, but proved significant for OS (p = 0.01). Significant radiobiological factors: the safety margin (expressed by the ratio treated surface on tumoral surface > or = 1.2) is significant for LC and OS. This is the same if the interval between EBI and Br is < or = 20 days. Neither the dose rate, the spacing between the sources, the total dose, nor Br dose were significant, but the last two were adapted according to the infiltration. In the univariate study for grade 2 and 3 complications (tissue and bone), the surface treated (> 12 cm2), and the dose rate > 0.7 Gy/h were significant. CONCLUSION The multivariate study showed that the small size of the lesion is the most important factor for local control, with brachytherapy alone for T1T2N0 and the number of days between EBI and brachytherapy < or = 20 days. For the complications, the most important factors are the total dose > 80 Gy and a treated surface > 12 cm2.

Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: Results in 73 cases

PURPOSE The salvage brachytherapy performed in patients presenting velotonsillar carcinoma in a previously irradiated field is evaluated in terms of local control, complications and survival. METHODS AND MATERIALS Between 1976 and 1990, 73 patients presenting with velotonsillar squamous cell carcinoma in a previously irradiated area were treated at Center Alexis Vautrin with brachytherapy along using an 192Ir implant (afterloading technique) with curative intent. According to the UICC 1987 TNM classification, there were 45 T1 N0, 20 T2 N0, one T3 NO, one T3 N2 and six Tx Nx. RESULTS The 5-year actuarial local control for T1 N0 and T2 N0 are 80% and 67% respectively. The regional relapse rate was 10% in both groups. Grade 2 complications occurred in 13% of patients and these were neither related to the volume treated nor the dose rate. There were no Grade 3 or 4 complications. The 5-year specific survival is 64%, with a plateau after the 5th year, but the 5-year overall survival is only 30%. Fourty-two percent of the patients in this series died from another carcinoma. All but two of these were related to continued alcohol and tobacco intoxication. CONCLUSION We conclude that brachytherapy alone (60 Gy) is optimal treatment for patients presenting with velontonsillar carcinoma in a previously irradiated field. The greatest challenge is the screening of these patients and the prevention of subsequent head and neck cancers. Recognizing the fact that these patients are at high risk for subsequent malignancies of upper aerodigestive tract, lung and esophagus, close surveillance is necessary for: (a) early diagnosis and prompt treatment; and (b) development of prevention strategies of field cancerization.

Role of interstitial brachytherapy in oral and oropharyngeal carcinoma: reflection of a series of 1344 patients treated at the time of initial presentation.

Our study focuses on a series of 1344 cases of carcinoma of the oral cavity and oropharynx treated between 1973 and 1992. Brachytherapy was always performed with iridium 192, either alone or in combination with external-beam irradiation or with surgery for the treatment of the primary tumor. For the oral cavity, we studied 565 cases of mobile tongue. The local control and overall survival rates, respectively, at 5 years are as follows: for T1, 92% and 70%; for T2, 62% and 42%; and for T3, 50% and 29%. For the subgroup T1T2NO, there was a better prognosis for treatment by brachytherapy of the primary lesion alone (p < 0.0001). Two hundred seven cases of floor-of-mouth carcinoma have been reported. The T3T4 patients were not considered surgical candidates. The local control and overall survival rates, respectively, at 5 years are as follows: for T1, 97% and 71%; for T2 72% and 42%; and for T3, 51% and 35%. Ninety-seven patients were treated by postoperative brachytherapy. These were patients for whom the margins after surgery were positive or narrow. A technique termed the modified bridge is described for lesions located in the mandible. Carcinomas of the buccal mucosa are rare in our country; only 42 cases were treated in this comparison of two techniques, and the overall survival rate was 48%. Epidermoid carcinomas of the oropharynx have nearly always been treated by a combination of external-beam irradiation and brachytherapy because of the bilateral node risk. Seventy-two patients with epidermoid cancers of the base of the tongue had an overall survival rate of 44%. The tonsil, soft palate, and pillars benefited from the use of the loop technique of brachytherapy combined with external-beam irradiation. Three hundred sixty-one patients were treated. Among these patients were two groups with different prognoses. Patients with tonsil, soft palate, and posterior pillar carcinomas had a local control rate of 84% and an overall survival rate of 57%. Conversely, the anterior pillar and the pharyngoglossal sulcus have a local control rate of only 65% and an overall survival rate of 38%. Statistical analysis revealed the prognostic factors for local control. The complications were classified into four grades: minor (20%), moderate (9%), major (4%), or inducing death (0.2%). The bone complications of grade 2 or 3 are more frequent for the floor of the mouth than for other locations.

Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques

Our purpose is to analyse local control, complications relative to the proportion of total dose delivered by external beam irradiation versus interstitial implant in 147 patients with previously untreated T2N0 squamous cell carcinoma of the oral tongue, managed between 1973 and 1986 (UICC staging system). These T2N0 patients are part of a larger group of 430 patients with oral tongue carcinoma (T1, T2, T3) treated with irradiation alone. Of these 147 T2N0 patients, 70 were treated with interstitial implant alone and 77 with both external beam irradiation and implant. In the group treated with interstitial implant alone, the 5-year local control was 89.8% against 50.6% in those treated with external beam irradiation and interstitial implant (log-rank test, p = 0.00002); 67.6% versus 46.5% for locoregional control (p = 0.029); and 62.2% versus 34.7% for specific survival (p = 0.0015). Since 1980, all the patients treated by iridium implantation were protected with a leaded spacing device between the tongue and the mandible. Soft tissue necrosis and bone exposure following treatment were scored according to the following criteria: minor, moderate or severe. Seven moderate and one severe complications were recorded in the brachytherapy group. None of the patients required surgery. In the combined treatment group, six moderate and two severe complications were observed. Patients treated with interstitial implant alone, and showing moderate or severe complications had received an average brachytherapy dose of 7600 cGy. In the same group, the patients without complications had received an average dose of 6800 cGy.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients)

PURPOSE To study the rate and severity of complications in a series of 1134 patients treated by definitive irradiation for tumors of the oral cavity (772 cases) or the oropharynx (361 cases). METHODS AND MATERIALS Patients were staged as 29.5% T1, 42% T2, 26% T3, 2.5% T4-Tx, and 74.5% N0 tumors. We treated 364 patients with brachytherapy only (192Ir) for the primary lesion. External irradiation and brachytherapy were combined for 770 patients. RESULTS The results included local control and survival. Out of 1134 patients, 330 had 376 complications. Grade 1 complications occurred in 20% of the patients, Grade 2 in 9%; Grade 3 in 4%; and Grade 4 in 0.2%. Of the Grade 1 complications, 78% were soft tissue and only 24% were bone complications. For the more severe grades (2, 3, and 4), there were 56 soft tissue complications and 90 bone complications out of 1340 patients. The statistical analysis included tumor-related factors and treatment-related factors. For the first two factors, only tumor location was significant. The treatment-related factors significant for complications were studied in univariate and multivariate study. This multivariate study confirmed that for soft tissue complications dose rate and volume treated were important (p < 0.001). It also confirmed that for bone complications, total dose > 80 Gy, dose rate > 0.7 Gy/h, and the absence of leaded protection of the mandible were all important factors. CONCLUSION This statistical study should allow future reduction of severe complications (Grades 2, 3, 4), if treatment factors inducing them can be taken into account. This is not always possible for very large tumors.

Influence of tumoral, radiobiological, and general factors on local control and survival of a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam irradiation + brachytherapy or brachytherapy alone)

PURPOSE To evaluate statistically the factors influencing the therapeutic results. METHODS AND MATERIALS A statistical study was carried out concerning 361 patients treated from 1977 to 1991 for velotonsillar carcinoma. They received either brachytherapy alone (18) or a combination of external beam irradiation and brachytherapy (343 patients) using an afterloading iridium technique in plastic tubes. The distribution of patients according to the localization was: 128 tonsils, 134 soft palates, 9 posterior pillars, 63 anterior pillars, and 27 glossotonsillar sulcus. The patients were staged as follows: 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3, and 9 Nx. RESULTS The results at 5 and 10 years show: local control 80% and 74%, locoregional control 75% and 70%, overall survival 53% and 27%, specific survival 63% and 52%, respectively. The univariate study shows at 5 years a better local control for T1T2 (87%) compared with T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (55%) with p = 0.002. This is the same for the overall survival (59% vs. 42%, p = 0.002). Tumors with an extension to the mobile tongue or the base have a poor prognosis (p < 0.002). The radiobiological factors show less recurrences if the total duration of the treatment is < 55 days, the number of days between External Beam Irradiation and brachytherapy is < 20. The security margin seems important also. CONCLUSIONS For the combination external irradiation and brachytherapy, the multivariate study for local control shows that ony T, localization, and the total duration of treatment are significant. For complications, classified into four grades, only the dose rate is significant.

A comprehensive analysis of the IMRT dose delivery process using statistical process control (SPC).

The aim of this study is to introduce tools to improve the security of each IMRT patient treatment by determining action levels for the dose delivery process. To achieve this, the patient-specific quality control results performed with an ionization chamber--and which characterize the dose delivery process--have been retrospectively analyzed using a method borrowed from industry: Statistical process control (SPC). The latter consisted in fulfilling four principal well-structured steps. The authors first quantified the short-term variability of ionization chamber measurements regarding the clinical tolerances used in the cancer center (+/- 4% of deviation between the calculated and measured doses) by calculating a control process capability (C(pc)) index. The C(pc) index was found superior to 4, which implies that the observed variability of the dose delivery process is not biased by the short-term variability of the measurement. Then, the authors demonstrated using a normality test that the quality control results could be approximated by a normal distribution with two parameters (mean and standard deviation). Finally, the authors used two complementary tools--control charts and performance indices--to thoroughly analyze the IMRT dose delivery process. Control charts aim at monitoring the process over time using statistical control limits to distinguish random (natural) variations from significant changes in the process, whereas performance indices aim at quantifying the ability of the process to produce data that are within the clinical tolerances, at a precise moment. The authors retrospectively showed that the analysis of three selected control charts (individual value, moving-range, and EWMA control charts) allowed efficient drift detection of the dose delivery process for prostate and head-and-neck treatments before the quality controls were outside the clinical tolerances. Therefore, when analyzed in real time, during quality controls, they should improve the security of treatments. They also showed that the dose delivery processes in the cancer center were in control for prostate and head-and-neck treatments. In parallel, long-term process performance indices (P(p), P(pk), and P(pm)) have been analyzed. Their analysis helped defining which actions should be undertaken in order to improve the performance of the process. The prostate dose delivery process has been shown statistically capable (0.08% of the results is expected to be outside the clinical tolerances) contrary to the head-and-neck dose delivery process (5.76% of the results are expected to be outside the clinical tolerances).