A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy.

OBJECTIVES: To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). PATIENTS AND METHODS: Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analysis (MVA) were performed. RESULTS: Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. CONCLUSION: Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.

Salvage Low Dose Rate Brachytherapy For Recurrent Prostate Cancer After External Beam Radiotherapy: Results From A Single Institution With Focus On Toxicity And Functional Outcomes.

BACKGROUND/AIM: Low dose rate brachytherapy has been used as salvage therapy for locally recurrent prostate cancer (PC) after primary external beam radiation therapy (EBRT), along with surgery and cryotherapy. All these techniques, in particular, when applied to the whole gland, involve a relatively high risk of toxicity and may worsen the patient's quality of life. Our aim is to evaluate the results of whole-gland salvage brachytherapy (SBT) after primary EBRT in terms of toxicity, functional outcomes, and efficacy. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 19 patients consecutively treated with SBT at our institution between June 2012 and November 2015. Local recurrences were identified with 11C-choline positron emission tomography/computed tomography and pelvic magnetic resonance imaging after biochemical recurrence according to Phoenix criteria (prostate-specific antigen nadir + 2). Low dose rate brachytherapy was performed by 125I permanent seeds implantation to the whole prostate gland, with a prescription dose of 130 Gy. At the time of SBT, only 2 patients were receiving androgen deprivation therapy. Acute and late toxicities were recorded using the CTCAE 4.0 scoring system. Quality of life was assessed using IPSS (International Prostate Symptoms Score) and IIEF (International Index of Erectile Function) questionnaires at baseline and 6, 12, and 24 months after SBT, and the respective mean values were compared using Student t test. Biochemical relapse-free survival (BRFS) was also calculated. RESULTS: Median follow-up after SBT was 24 months. Of 19 patients, 2 patients experienced a G3 cystitis (10.2%) and 1 patient experienced a G4 proctitis (5.3%), respectively. Mean pre-SBT IPSS scores and 6, 12, and 24 months after SBT were 5.84, 10.22, 15.72, and 8.10, respectively. Mean pre-SBT IIEF scores and 6, 12, and 24 months after SBT were 8.42, 3.55, 7.89, and 6.40, respectively. At the time of analysis, only 2 patients showed a biochemical relapse (3-year BRFS 85.2%). The Student t test demonstrated a worsening of functional outcome 6 months and 1 year after treatment but a subsequent improvement 2 years after SBT. CONCLUSIONS: Salvage brachytherapy for recurrent PC after primary EBRT seems to be a feasible treatment for selected patients. Our series revealed a severe toxicity peak 6 months and 1 year after local re-treatment and then they decrease. Early BRFS rates are good. However, these are very preliminary results so further patient accrual, long-term follow-up, and prospective trials are needed in the future.

Nasopharyngeal carcinoma in a low incidence European area : A prospective observational analysis from the Head and Neck Study Group of the Italian Society of Radiation Oncology (AIRO).

PURPOSE: To evaluate the outcomes with respect to long-term survival and toxicity in patients with nasopharyngeal carcinoma (NPC) treated in a European country with low incidence. MATERIALS AND METHODS: A prospective observational study carried out by the AIRO Head and Neck group in 12 Italian institutions included 136 consecutive patients treated with radiotherapy (RT) ± chemotherapy (CHT) for NPC (without distant metastasis) between January 1, 2008 and December 31, 2010. RESULTS: The disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) at 5 years were 92 (±2), 91 (±3), and 69 % (±5 %), respectively. Distant failure was the most frequent modality of relapse. The local, regional, and locoregional control at 5 years were 89 (±3), 93 (±3), and 84 % (±4 %), respectively. The incidence of acute and late toxicity and the correlations with different clinical/technical variables were analyzed. Neoadjuvant CHT prolongs radiotherapy overall treatment time (OTT) and decreases treatment adherence during concomitant chemoradiotherapy. An adequate minimum dose coverage to PTV(T) is a predictive variable well related to outcome. CONCLUSION: Our data do not substantially differ in terms of survival and toxicity outcomes from those reported in larger series of patients treated in countries with higher incidences of NPC. The T stage (TNM 2002 UICC classification) is predictive of DSS and OS. The GTV volume (T ± N) and an adequate minimum PTV(T) coverage dose (D95 %) were also identified as potential predictive variables. Sophisticated technologies of dose delivery (IMRT) with image-guided radiotherapy could help to obtain better minimum PTV(T) coverage dose with increased DFS; distant metastasis after treatment still remains an unresolved issue.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis.

PURPOSE OF INVESTIGATION: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT). MATERIALS AND METHODS: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis. RESULTS: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques. CONCLUSIONS: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

Role of external beam radiotherapy in the treatment of relapsing meningioma.

The role of radiotherapy in the treatment of relapsing meningiomas is not well established. Data of patients treated with radiotherapy for a relapsing meningioma were retrospectively analyzed. Overall survival (OS) was the primary endpoint of the analysis. Local control and acute and late toxicity rates have been also reported. From April 1986 to February 2011, 37 patients with a diagnosis of recurrent meningioma were treated. Median age was 64 years (range 36-79). A total of 18, 10, 5 and 4 patients were affected by relapsing benign, atypical, malignant meningiomas and meningiosarcomas, respectively (WHO classification). Median dose was 60 Gy (range 46-66 Gy). The median follow-up was 42 months (range 3-300 months). OS at 1, 3, 5 and 8 years was 81, 55.6, 43.9 and 25.8%, respectively (median OS 45 months). A strong statistical trend was observed toward better OS rates in patients treated with radiotherapy at first recurrence compared to those treated at the second (or more) recurrence (OS 50.5 vs. 30.8%, p=0.055). A statistical impact of the histology (WHO I vs. II, III and IV) on 5-year OS was also observed (OS 60 vs. 30%, 0 and 0%, p=0.010). Radiotherapy has been well tolerated, with no G2-4 neurological toxicity (RTOG toxicity score). Conventional radiation therapy has an important role in multidisciplinary approach in the treatment of recurrence of meningiomas. The histological type and the timing of the radiotherapy are prognostic factors in terms of survival.

Clinical similarities: an innovative approach for supporting medical decisions.

Taking decisions in the medical domain is a very complex task. The context is strongly affected by uncertainty and the possible undesired side effects of the treatments have to be carefully considered. Currently, these decisions are based on the physician's own experience and the evidences of the published literature, according, when available, with the philosophy of Evidence Based Medicine. The main issues of this approach are that the own experience can be different, and the results in the literature are sometimes contrasting. For helping physicians while taking medical decisions, we are proposing an innovative approach based on the idea of the clinical similarity. Given a set of clinical variables, the proposed approach selects patients that are similar, presenting to the physician the respective decisions taken and the corresponding clinical effects.

In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: results of a multicentre observational study.

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates.

Adjuvant intensity-modulated proton therapy in malignant pleural mesothelioma. A comparison with intensity-modulated radiotherapy and a spot size variation assessment.

PURPOSE: Intensity-modulated radiation therapy (IMRT) is the state-of-the-art treatment for patients with malignant pleural mesothelioma (MPM). The goal of this work was to assess whether intensity-modulated proton therapy (IMPT) could further improve the dosimetric results allowed by IMRT. PATIENTS AND METHODS: We re-planned 7 MPM cases using both photons and protons, by carrying out IMRT and IMPT plans. For both techniques, conventional dose comparisons and normal tissue complication probability (NTCP) analysis were performed. In 3 cases, additional IMPT plans were generated with different beam dimensions. RESULTS: IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity (p < 0.001) and dose homogeneity (p = 0.01). Better organ at risk (OAR) sparing was obtained with IMPT, in particular for the liver (D(mean) reduction of 9.5 Gy, p = 0.001) and ipsilateral kidney (V(20) reduction of 58%, p = 0.001), together with a very large reduction of mean dose for the contralateral lung (0.2 Gy vs 6.1 Gy, p = 0.0001). NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus (average NTCP 14% vs. 30.5%) and the ipsilateral kidney (p = 0.001). Concerning plans obtained with different spot dimensions, a slight loss of target coverage was observed along with sigma increase, while maintaining OAR irradiation always under planning constraints. CONCLUSION: Results suggest that IMPT allows better OAR sparing with respect to IMRT, mainly for the liver, ipsilateral kidney, and contralateral lung. The use of a spot dimension larger than 3 × 3 mm (up to 9 × 9 mm) does not compromise dosimetric results and allows a shorter delivery time.

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part I: Evolving technical choices and survival.

PURPOSE: The authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease-specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local-regional control (LRC) probability. RESULTS: At univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS. CONCLUSIONS: Results of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity-modulated radiotherapy (IMRT).

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part II: Evolving technical choices and toxicity patterns.

PURPOSE: The authors sought to define toxicity patterns according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared. RESULTS: Higher total and fractional doses and the "older" treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications. CONCLUSIONS: Results of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity-modulated radiotherapy (IMRT) for NPC patients.

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.

Late computed tomography scan response improvement and gallium scintigraphy evaluation as on-treatment prognostic parameters to tailor treatment intensity in patients with Hodgkin's lymphoma. A prospective phase II study.

BACKGROUND: Tailoring treatment intensity is critical in Hodgkin's lymphoma (HL). Ongoing prognostic parameters may be an useful adjunct to pretreatment stratification. We used the kinetics of computed tomography (CT) scan response and residual gallium (Ga)-67 uptake to better stratify risk. MATERIALS AND METHODS: Patients received 4-8 adriamycin, bleomycin, vinblastine and dacarbazine courses according to stage. Disease was reassessed evaluating late computed tomography scan response improvement (CTRI) and Ga-67 uptake. Patients received no further treatment, radiotherapy (RT) or additional chemotherapy + RT according to the presence of none (low risk), one (intermediate risk) and both parameters (high risk). Patients with bulky mediastinum received RT anyhow. RESULTS: Among 102 assessable patients, 35 showed late CTRI and 9 residual Ga-67 uptake. In 30 patients with bulky mediastinum, the 3-year progression-free survival (PFS) was significantly better when neither parameter was present (100% versus 69%; P = 0.02). In 72 patients without bulky mediastinum, treatment was tailored according to risk assignment. Relapses occurred in 5 of 47 low-risk and 3 of 21 intermediate-risk patients, with no differences between the two groups, and in 3 of 4 high-risk patients. CONCLUSION: This study shows that two on-treatment parameters, late CTRI and residual Ga-67 uptake, can predict PFS in HL and identify patients in which RT can be spared without apparently affecting the outcome.

Open-source, low-cost, high-reliability solutions for digital imaging systems: example of a "dicom router".

PURPOSE: The purpose of this article is to illustrate a case where acquisition of digital imaging know-how by a modern radiotherapy division has helped to solve a technical problem while allowing substantial savings through the use of free and open-source resources. The problem was related to the necessity to route, with complex policies, the images produced by different digital imaging and communications in medicine (DICOM) sources within the department or in other divisions and/or hospitals. MATERIALS AND METHODS: The problem was solved by using completely free, well-tested and stable technologies (PHP, Apache, MySQL, DCMTK OFFIS, Red Hat Linux 9A and Linux Fedora Core 4) and low-cost hardware to contain costs. In the development, we also considered integration of the routed images with the existing electronic clinical records. RESULTS: The system developed, called the dicom router, implemented two kinds of routing: manual and automatic, both oriented to link the images acquired with the existing electronic clinical records. System stability was enhanced in a second phase by using a low-cost hardware redundancy solution. The system has now been operating for 1 year and has proved the value of the technologies used. CONCLUSIONS: The need to operate with more than one provider creates a series of integration issues, so that it becomes economically appealing to acquire internally the knowledge needed to interact more precisely with providers of big information technology (IT) solutions. This need is well catered for by open-source technologies, which are well documented and available to everyone. By using them, in-house IT technicians are able to implement valuable technical solutions for small-to medium-sized informatization problems, which would otherwise remain unsolved except with great economic efforts.

Postoperative radiotherapy after radical prostatectomy for prostate carcinoma: the experience of the Brescia Radium Institute.

PURPOSE: The purpose of this study was to evaluate the efficacy of postoperative radiotherapy in reducing the incidence of prostate carcinoma (PCa) recurrences after radical prostatectomy (RP), define the importance of the time interval between surgery and radiotherapy for prognosis and the toxicity of the treatment in comparison with radiotherapy or surgery alone. MATERIALS AND METHODS: We examined 97 patients who consecutively underwent postoperative radiotherapy after RP between 1980 and 2003. The treatment was considered "adjuvant" if was conducted less than 6 months after RP, if there was no macroscopic residual disease and if there was no progressive increase in serum prostate-specific antigen (PSA) and "salvage" if performed more than 6 months after RP, for the presence of macroscopic recurrence or with rising PSA. Radiotherapy was salvage in 56 patients and adjuvant in 41. Age range was 60-70 years in 80% of patients, and the Karnofsky index was over 80 in 78% of cases. Histology revealed extracapsular spread in 60% of patients. Preradiotherapy PSA was higher than 1 ng/ml in 36%. Radiotherapy was performed on the surgical bed only in 80%, and the total dose was 70 Gy in 62% of cases. RESULTS: Recurrence-free survival (RFS) at 5 years and 10 years was 53+/-8% and 32+/-14.2%, respectively, for the whole sample; 76+/-9% and 38+/-2.7% for patients treated with adjuvant radiotherapy and 36+/-10% and 28+/-10% for those treated with salvage radiotherapy (p<0.01). Moreover, the 5-year RFS was better in the group treated with adjuvant radiotherapy and PSA less than or equal to 1 ng/ml (p<0.05). Treatment toxicity was acceptable. CONCLUSIONS: Postoperative radiotherapy improves RFS and reduces the risk of local recurrence. The best results are obtained with early postoperative treatment ("adjuvant"); adjuvant radiotherapy of high-risk forms yields better results if performed with PSA less than or equal to 1 ng/ml.

Radical radiotherapy for bladder cancer: retrospective analysis of a series of 459 patients treated in an Italian institution.

AIMS: To contribute to the available evidence about the efficacy of exclusive radiotherapy for bladder cancer through a retrospective analysis of a large series of patients consecutively treated in a single institution. MATERIALS AND METHODS: A total of 459 patients with UICC categories T1-T4, N0-Nx and M0 bladder cancer consecutively treated with radiotherapy alone with radical intent formed the clinical basis for this study. Many of them (and particularly the T1 cases) had poor medical conditions or were unfit for surgery. About half of the cases (54%) had a T2 tumour, and about 18% had T3-T4 disease. Eighty per cent of the cases received minimal doses in the target volume in the range 60-70 Gy; pelvic lymph nodes were treated in 34%. Simple radiotherapy techniques were used in most cases. Average follow-up for living patients was 4.4 years. Results were analysed according to number and type of relapses: overall survival, disease-specific survival, failure-free survival probability, acute and late toxicity (RTOG scale). RESULTS: Actuarial 5-year overall survival, disease-specific survival and failure-free survival rates at 5 years for the entire series were 36%, 56%, 33%, respectively. Age, T category (for all the end points) and tumour dose (only for failure-free survival) were significantly related to prognosis at multivariate survival analysis. Late enteric toxicity (6.1% of the cases) was significantly linked with the treated volumes (univariate analysis). Urinary late toxicity (23% of cases) was linked with age and T category (multivariate analysis). In both cases, toxicity was mostly Grade 1 or 2. CONCLUSIONS: The results of radiotherapy in this negatively selected series, accrued over a long period of time in patients treated with unsophisticated techniques, are reasonably good; they add to the evidence available to support the use of modern bladder-sparing programmes, including the association of chemo- and radiotherapy.

Stage I seminoma of the testis: a bi-institutional retrospective analysis of patients treated with radiation therapy only.

OBJECTIVE: To analyse relapse patterns, toxicity and second malignancy in patients with stage I pure germ cell testicular tumours, treated in 1970-1999. PATIENTS AND METHODS: In all, 487 patients received irradiation after surgery to the infra- (407, 83.5%) or infra- and supra-diaphragmatic volumes (80, 16.5%). Treatment-related toxicity was classified according to previous criteria and fertility investigated in 246 men. Second malignancies were identified by retrospective analysis of clinical records or telephone interviews in men who no longer needed a long-term follow-up. RESULTS: The 10-year overall survival was 97% (98% and 96%, respectively, for the aortic nodes only, or aortic and iliac nodes, i.e. the 'dog leg' field) and disease-free survival was 94%. Twenty-one patients relapsed (five with a true 'in-field' recurrence, nine progressed to the mediastinum, and seven had disseminated disease). Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade II. In all, 73 men achieved paternity after irradiation; nine did not but had normal sperm. Second malignancies were diagnosed in 16 (3.3%) men. CONCLUSION: Para-aortic irradiation may be used safely in patients with stage I seminoma and undisturbed testicular drainage, with equivalent results to the 'dog-leg' group; these unrandomized data confirm the lower toxicity and equivalent survival rates of this treatment.

Breast cancer occurred after treatment for Hodgkin's disease: analysis of 133 cases.

PURPOSE: To assess the clinical and histological characteristics of breast cancer (BC) occurring after Hodgkin's disease (HD) and give possible therapies and prevention methods. MATERIALS AND METHODS: In a retrospective multicentric analysis, 117 women and two men treated for HD subsequently developed 133 BCs. The median age at diagnosis of HD was 24 years. The HD stages were stage I in 25 cases (21%), stage II in 70 cases (59%), stage III in 13 cases (11%), stage IV in six cases (5%) and not specified in five cases (4%). Radiotherapy (RT) was used alone in 74 patients (63%) and combined modalities with chemotherapy (CT) was used in 43 patients (37%). RESULTS: BC occurred after a median interval of 16 years. TNM classification (UICC, 1978) showed 15 T0 (11.3%), 44 T1 (33.1%), 36 T2 (27.1%), nine T3 (6.7%), 15 T4 (11.3%) and 14 Tx (10.5%). Ductal infiltrating carcinoma and ductal carcinoma in situ (DCIS) represented 81.2 and 11.3% of the cases, respectively. Among the infiltrating carcinoma, the axillary involvement rate was 50%. Seventy-four tumours were treated by mastectomy without (67) or with (ten) RT. Forty-four tumours had lumpectomy without (12) or with (32) RT. Another four received RT alone, and one CT alone. Sixteen patients (12%) developed isolated local recurrence. Thirty-nine patients (31.7%) developed metastases and 34 died; 38 are in complete remission whereas five died of intercurrent disease. The 5-year disease-specific survival rate was 65.1%. The 5-year disease-specific survival rates for the pN0, pN1-3 and pN>3 groups were 91, 66 and 15%, respectively (P<0.0001), and 100, 88, and 64% for the TIS, T1 and T2. For the T3 and T4, the survival rates decreased sharply to 32 and 23%, respectively. These secondary BC are of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN>3 and/or T3T4), and many tumours with a 'slow spreading' such as DCIS and microinvasive lesions. These lesions developed especially in patients treated exclusively by RT. CONCLUSIONS: The young women and girls treated for HD should be carefully monitored in the long-term by clinical examination, mammography and ultrasonography. We suggest that a baseline mammography is performed 5-8 years after supradiaphragmatic irradiation (complete mantle or involved field) in patients who were treated before 30 years of age. Subsequent mammographies should be performed every 2 years or each year, depending on the characteristics of the breast tissue (e.g. density) and especially in the case of an association with other BC risk factors. This screening seems of importance due to excellent prognosis in our T(1S)T(1) groups, and the possibility of offering these young women a conservative treatment.