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Background: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. Patients and Methods: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. Results: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6–6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. Conclusions: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Purpose The Deep Inspiration Breath Hold (DIBH) technique was introduced in order to freeze the breathing motion in a mid-inhale position with a computer controlled valve, with the purpose of lowering heart dose in left breast radiotherapy. A training project with FMECA analysis was started, aiming to write and implement a protocol, improved by proactive clinical risk analysis and feedback from the operators (radiotherapists, radiographers and medical physicists). Methods and materials At first, few operators were involved to take knowledge and dexterity with the system. They became the tutors and the core of the improvement group for the subsequent training project. The project was comprised of four stages: (1) implementation of the technique (tutors); (2) field training (tutors and operators); (3) training course on FMEA/FMECA analysis (all operators and clinical governance department); (4) implementation of the FMECA analysis in left breast radiotherapy DIBH treatments (tutors and FMEA-workgroup; the FMEA workgroup consisted of these professional roles: radiotherapists, radiographers, medical physicists and clinical governance area’s physicians). Results The outputs for each stage were: (1) redact the protocol and the training checklist; (2) training of all operators and application of the self-evaluation checklist; (3) understanding the clinical risk principles; (4) application of the FMEA analysis, data processing and final report. The self-evaluation checklist was comprised of 37 targets, with achieved/partially-achieved/not-achieved check boxes. The FMEA table was comprised of 48 activities, subdivided in 5 phases (DIBH-suitable-patients detection, treatment simulation, planning, radiotherapy treatment delivery, quality control), with pertinent Risk Probability Numbers associated. Points 1–3 were completed, while completion of point 4 is expected for the first half of 2018. Conclusion The application of the FMEA/FMECA method allowed us to introduce proactive methods to analyze and manage the clinical risk related to the introduction of the new DIBH technique. The FMEA/FMECA method was included in a training project which allowed to obtain feedback from all the involved operators, improving the understanding of the work process, the skill and safety in the practical use and the redaction of a multidisciplinary protocol.

It has recently been reported that the incidence of brain metastases (BMs) from prostate cancer (PC) has increased in comparison with historical series. The aim of this study was to compare the incidence of BMs in the pre- and post-docetaxel era in a single institution in which all oncological patients are referred to one Radiotherapy and one Medical Oncology Department. We searched the electronic databases of these departments for all males with BMs entered from 1994 to 2011. The year of the introduction of docetaxel into clinical practice (2002) divided the observation period into two 9-year periods: period 1 (P1) from 1994 until 2002 (P1), and period 2 (P2) after 2002. The number of patients with BMs was constant: 241 patients in P1 and 249 in P2. The greatest changes in frequency between P1 and P2 involved colorectal cancer (+75.9 %), renal cancer (+141.9 %), and PC (+238.7 %). The total number of patients with BMs from PC was nine: two in P1 (0.8 %) and seven in P2 (2.8 %). All but two of these patients developed BMs after becoming castration-resistant. Median BM-free survival was 36 months, whereas median BM survival was 8 weeks. As the appearance of BMs in the natural history of PC is usually related to the late phase of the disease, and mortality due to PC remained constant, it seems that there really has been an increase in the frequency of BMs from PC that may reflect a gain in survival.

BACKGROUND: Cystectomy is the standard treatment for patients with infiltrating bladder cancer, but conservative treatment with cystoscopic resection followed by radiochemotherapy may be an alternative for highly selected patients. The addition of gemcitabine to cisplatin and radiotherapy may enhance disease control. METHODS: The long-term clinical outcomes of 26 patients enrolled in a previously published dose-finding study and a prematurely discontinued phase 2 trial were evaluated. All the patients underwent transurethral tumor resection followed by a radical dose of external radiotherapy administered at the same time as cisplatin and weekly gemcitabine therapy. RESULTS: After a median follow-up of 74 months, the projected 5-year clinical outcomes were a 70.1% overall survival rate, a 78.9% disease-specific survival rate, and a 73.8% bladder-intact survival rate. CONCLUSIONS: The long-term follow-up data from the current study confirmed that the addition of gemcitabine to radiotherapy and cisplatin is safe and leads to good local and distant disease control. The concomitant administration of cisplatin may explain the good long-term organ preservation that was observed. Conducting confirmatory and comparative trials could satisfy an unmet need but requires the multidisciplinary cooperation of urologists in selecting the right patients for a bladder-sparing strategy. Cancer 2011. © 2010 American Cancer Society.

Serum selenium levels were measured in 38 patients with malignant lymphoproliferative diseases (MLD) and in 34 non-hospitalized healthy individuals. Selenium was determined by proton induced x-ray emission. In Hodgkin's disease and non-Hodgkin malignant lymphoma the mean serum levels of selenium were not different from those of the control group. On the contrary lowered mean serum selenium concentrations were observed in the group with chronic lymphocytic leukaemia (5.2 +/- 0.7 microgram/100 ml) as compared to normal individuals (7.9 +/- 0.3 microgram/100 ml). The difference is highly significant (P less than 0.005). A second selenium test was made in 11 out of the 38 patients within 8 weeks from the beginning of radiotherapy or chemotherapy; unchanged levels were found.

Background To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT). Materials and methods We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient. Results QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy. Conclusions The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced.

Purpose: Permanent interstitial brachytherapy (IB) has become an increasingly appealing therapeutic option for localized prostate cancer (LPC) among physicians and patients because it involves short hospitalization and treatment and its postulated low degree of toxicity may reduce its impact on the patients’ quality of life (QoL). The aim of this prospective study was to assess the impact of IB on the QoL of patients with LPC. Methods and Materials: A validated self-completed questionnaire was administered to the patients before and after IB and then at yearly intervals. The items allowed the identification of seven subscales exploring physical well-being (PHY), physical autonomy (POW), psychological well-being (PSY), relational life (REL), urinary function (URI), rectal function (REC), and sexual function (SEX). Results: The assessment of the QoL of 147 patients treated between May 2000 and February 2005 revealed no relevant differences in the PHY scale scores 1 month after IB or later, and the same was true of the POW, PSY, and REL scales. Urinary function significantly worsened after IB and returned to pretreatment levels only after 3 years; the impact of the treatment on the URI scale was greater in the patients with good baseline urinary function than in those presenting more urinary symptoms before IB. Rectal and sexual functions were significantly worse only at the post-IB evaluation. Conclusions: The results of the present study confirm that the impact of IB on the patients’ QoL is low despite its transient negative effects on some function, and extend existing knowledge concerning QoL after IB.

A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

e20594Background: BM development, which is frequently observed in pts with NSCLC, is usually associated with a poor outcome. Systemic treatments and whole brain radiotherapy (WBRT) are widely used ...

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

Fifty-six patients with superior sulcus syndrome were evaluated at the First Surgical Department of the University of Padua between 1981 and 1990. Forty-two patients with the characteristic of Pancoast's tumor received preoperative irradiation and then en bloc resection of the tumor, chest wall, and adjacent structures. Seven lobectomies and 35 segmentectomies or wedge resections were performed. There was one early postoperative death. Median survival was 14 months, and actuarial survival was 25% at 5 years. Patients with pain relief had better 5-year survival (36.4%) than patients without pain relief (9%). We have no patients with vertebral invasion who survived more than 1 year. Of the five patients with subclavian artery invasion, only one survived more than 1 year. Of five patients with N2 disease, only one survived more than 1 year. Our results suggest that pain relief after irradiation is a good prognostic factor, whereas N2 involvement and vertebral body and great vessel invasion are ominous factors. Another ominous prognostic factor is the Claude Bernard-Horner syndrome even if it is not a contraindication to resection. (J T horac C ardiovasc S urg 1992;104:679-83)

Multiple primary neoplasia was once considered a rare curiosity but is now a well recognized phenomenon. Only a few papers have been published in the English literature with regard to occurrence of four or more primary malignancies in a single patient. We report four cases of quadruple cancer; a review of the literature about this topic is discussed.

BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

To estimate the dosimetric impact of residual setup errors on parotid sparing in head-and-neck (HN) intensity-modulated treatments and to evaluate the effect of employing an PRV (planning organ-at-risk volume) margin for the parotid gland.Ten patients treated for HN cancer were considered. A nine-beam intensity-modulated radiotherapy (IMRT) was planned for each patient. A second optimization was performed prescribing dose constraint to the PRV of the parotid gland. Systematic setup errors of 2 mm, 3 mm, and 5 mm were simulated. The dose-volume histograms of the shifted and reference plans were compared with regard to mean parotid gland dose (MPD), normal-tissue complication probability (NTCP), and coverage of the clinical target volume (V95% and equivalent uniform dose [EUD]); the sensitivity of parotid sparing on setup error was evaluated with a probability-based approach.MPD increased by 3.4%/mm and 3.0%/mm for displacements in the craniocaudal and lateral direction and by 0.7%/ mm for displacements in the anterior-posterior direction. The probability to irradiate the parotid with a mean dose30 Gy was50%, for setup errors in cranial and lateral direction and10% in the anterior-posterior direction. The addition of a PRV margin improved parotid sparing, with a relative reduction in NTCP of 14%. The PRV margin compensates for setup errors of 3 mm and 5 mm (MPDor = 30 Gy in 87% and 60% of cases), without affecting clinical target volume coverage (V95% and EUD variations1% and1 Gy).The parotid gland is more sensitive to craniocaudal and lateral displacements. A setup error of 2 mm guarantees an MPDor = 30 Gy in most cases, without adding a PRV margin. If greater displacements are expected/accepted, an adequate PRV margin could be used to meet the clinical parotid gland constraint of 30 Gy, without affecting target volume coverage.

Pancreatic cancer is a highly lethal disease either for the high incidence of distant metastases or for the frequent local recidive also after potentially curative resection. For this reason new multimodality approaches have to be investigated. Intraoperative radiotherapy (IORT) permits to administer a high dose to the tumor or to the retropancreatic tissues and to the regional lymphnodes. Literature data suggest it is possible a better local control and pheraps a better survival than the surgery alone or the palliative treatments by the use of schedules with IORT. Anyway they are retrospective data and IORT is an investigational method which has to be indagate in the combined modality approaches to this disease.

To investigate the feasibility of applying exclusive intraoperative radiation therapy (IORT) after conservative surgery in limited-stage breast carcinoma and to evaluate late effects and cosmetic results after this new conservative treatment. From October 2000 to November 2002, 47 consecutive patients with unifocal breast carcinoma up to a diameter of 2 cm received conservative surgery followed by IORT with electrons as the sole adjuvant local therapy. Three different dose levels were used: 20 Gy (seven patients), 22 Gy (20 patients), and 24 Gy (20 patients). Patients were evaluated using RTOG/EORTC scale to assess the incidence of late complications. During follow-up, a radiologic assessment with mammography and sonography was periodically performed and any breast-imaging alterations were reported. After a follow-up ranging from 36 to 63 months (median, 48 months), 15 patients developed breast fibrosis (grade 2 in 14 patients, grade 3 in one patient), two patients presented with grade 3 skin changes, one patient developed a clinically relevant fat necrosis, and one patient showed breast edema and pain. Two patients developed contralateral breast cancer and one distant metastases; no local relapses occurred. Asymptomatic findings of fat necrosis were observed at mammography in twelve patients (25.5%), while an hypoechoic area was revealed by sonography in ten patients (21.5%). In four patients (8%), mammographic and sonographic findings suggested malignant lesions and required a rebiopsy to confirm the benign nature of the lesion. IORT in breast carcinoma is still an experimental treatment option for select patients with breast cancer and its application should be restricted to prospective trials. Although preliminary data on local control are encouraging, a longer follow-up is needed to confirm the efficacy of IORT in breast cancer and to exclude that severe late complications compromise the cosmetic results or modify the radiologic breast appearance during follow-up increasing the need for additional investigations.

In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the long-term results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] = 15.3% to 30.9%) and 19% (95% CI = 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI = 9.6% to 23.4%) and 9% (95% CI = 3.5% to 14.7%), respectively, for those in group B (P = .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI = 14.9% to 47.3%] and 22.7% [95% CI = 7.1% to 38.3%], respectively; group B, 43.3% [95% CI = 25.6% to 61.0%] and 14.2% [95% CI = 0.1% to 28.3%], respectively; P = .73). Among inoperable patients, overall survival at 5 and 10 years was 21% (95% CI = 12.3% to 30.1%) and 16% (95% CI = 7.7% to 23.9%), respectively, for group A and 8% (95% CI = 1.5% to 12.3%) and 6% (95% CI = 0.1% to 9.1%), respectively, for group B (log-rank P = .04). Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease.

Purpose Although the use of radical transurethral resection followed by concurrent radiochemotherapy leads to a similar survival rate to that achieved after cystectomy, the number of long-term survivors is low in both cases. An improvement may be obtained by adding a new drug, such as gemcitabine, which is active in bladder cancer and acts as a radiosensitizer. However, because gemcitabine may be very toxic when associated with radiotherapy, we designed this dose-finding study in an attempt to find the dose that can be safely added to radiotherapy and concurrent cisplatin in patients treated with transurethral resection for infiltrating bladder cancer. Patients and methods After undergoing macroscopically complete transurethral resections for transitional carcinoma of the bladder, patients staged pT2 or higher and without distant metastases concurrently received 54 Gy of fractionated radiotherapy over 6 weeks with cisplatin (100 mg/m 2 q.3 w), starting on Day 1 of radiotherapy. Concomitant gemcitabine was administered on Days 1, 8, and 15 q.3 w for 2 cycles at a dose of 200 mg/m 2 , escalated to 500 mg/m 2 , with a 100 mg/m 2 increase at each dose level. The maximum tolerated dose was defined as the dose of gemcitabine associated with dose-limiting toxic effects (febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 or 4 enteric toxicity, or Grade 4 nonhematologic toxicity) in 33% of the patients treated at that dose level. Six to 8 weeks after completing the therapy, the patients underwent cystoscopic reevaluation with multiple biopsies of the initial tumor site. Results Of our consecutive series of 16 patients, 5 received a gemcitabine dose of 200 mg/m 2 /week, 3 a dose of 300 mg/m 2 /week, 3 a dose of 400 mg/m 2 /week, and 5 a dose of 500 mg/m 2 /week for 6 weeks. No dose-limiting toxicity was observed at doses of up to 400 mg/m 2 /week. At the dose 500 mg/m 2 /week, 1 patient experienced an intestinal perforation that recovered after surgery, and another suddenly died after developing Grade 3 untreated diarrhea in the last treatment week. All of the 15 evaluable patients were microscopically disease free at the cystoscopic reevaluation; furthermore, the posttreatment computed tomography scans did not reveal any distant metastases. Conclusions After transurethral resection for the conservative treatment of infiltrating bladder cancer, gemcitabine doses of up to 400 mg/m 2 /week seem to be safe in combination with cisplatin and radiotherapy in organ-sparing management. On the basis of the promising results of this Phase I study, we are currently conducting a Phase II trial to verify the possible improvement in local control resulting from the addition of gemcitabine.

Adjuvant pelvic radiotherapy (XRT) after radical surgery for uterine cancer may cause various (mainly gastrointestinal) side effects capable of affecting a patient's lifestyle. This prospective study used a diary card to evaluate toxicity and daily quality of life changes in uterine cancer patients given postoperative pelvic radiotherapy.The self-completed diary card listed 12 items concerning lifestyle changes and side effects. The patients were stratified by age (/=65 vs65 years).Twenty-five patients were evaluable, and a total of 848 days were assessed (82.6% of the 1027 days of XRT). The mean number of daily stools progressively increased during treatment (P0.01). No statistically significant differences were observed in terms of nausea or pain. There was a significant decrease in appetite (P0.01). Vaginal symptom scores did not significantly change during treatment, and no significant differences were found in terms of anxiety, daily activities, or compliance to therapy. The subjective perception of overall well-being and the quality of life score progressively and significantly decreased over time (P0.01). The younger patients had significantly more bowel movements, less appetite, more pain and vaginal burning, less vaginal bleeding, more anxiety, a greater reduction in daily activities and therapeutic compliance, a poorer subjective perception of overall well-being, and a lower quality of life score.The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of uterine cancer patients receiving postoperative radiotherapy.

PURPOSE: Adjuvant pelvic radiotherapy after radical surgery for rectal cancer may produce several side-effects (mainly gastrointestinal) capable of affecting patient lifestyle. This prospective study evaluated by means of a diary card the toxicity and daily changes in the quality of life of patients with rectal cancer treated with postoperative pelvic radiotherapy. METHODS: We used a diary card listing ten items about lifestyle changes and side-effects compiled by patients themselves. The patients were stratified by age (≤ 65 vs. > 65 years), the presence or not of a stoma, and the administration or not of concurrent chemotherapy. RESULTS: Twenty-seven patients were evaluable. The mean number of bowel movements increased across time, without statistically significant differences. Nausea and appetite did not significantly change during the treatment period. There was a statistically significant, progressive increase in the perception of pain (P < 0.03). Although not significantly, the anxiety scores were lower during radiotherapy than at baseline. Daily activities and compliance with therapy did not significantly change during the treatment. There was a significant worsening in overall well-being (P < 0.04) and quality of life evaluation (P < 0.03). The patients who received chemoradiotherapy experienced a worsened lifestyle and greater side-effects. Older patients experienced less pain but had statistically significant higher levels of anxiety. Patients with a stoma reported a better quality of life score than those without. CONCLUSIONS: The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of patients with rectal cancer treated by postoperative radiotherapy.

Background and purpose : Standard therapy in early-stage testicular seminoma (TS) includes inguinal orchiectomy followed by irradiation (XRT) of the pelvic and para-aortic nodes. Since this treatment is highly effective in controlling the disease and leads to many long survivors, the quality of life (QL) may be impaired by treatment-induced side-effects. The aim of this study was to provide a QL evaluation of patients treated with XRT after orchiectomy for TS. Materials and methods : We used a validated self-completed questionnaire based on a series of 44 items covering all QL fields. The items were grouped into six subscales with standardized scores. The questionnaire was mailed to a consecutive series of 143 patients treated between 1961 and 1995 for TS with no evidence of disease after primary treatment. Results : Ninety-eight questionnaires (68.5%) were returned and are assessable. The median age of the patients was 48 years (range, 26–85 years) at the time of completing the questionnaire, with a median follow-up after completion of treatment of 123 months (range, 15–432 months). The physical and autonomy subscale standardized scores were ≥1 in 83 and 95% of the cases, respectively. Psychological problems were reported by a small percentage of patients, ranging from 13, who reported a depressive condition, to 16%, who declared feeling tense. Of the patients, 86 and 89% have regularly met relatives and friends. The urinary score was above the central point in 99% of the patients. Only 6% of the patients perceived their body image as worsened by treatment. The patients who were more informed about the disease and therapy had a better physical and psychological adjustment. Conclusions : The QL in our patients resulted as satisfactory, with a maintained body image and few side-effects. The information given to the patients about their disease and its treatment influenced the post-treatment QL adjustment.

The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.

Choroidal metastasis from primaries other than breast or lung cancer is a rare event. There is no documented case in the literature of choroidal metastases in patients with hypopharynx carcinoma. Early treatment with radiation therapy provides effective palliation by preserving visual function and preventing the need for enucleation. Chemotherapy alone does not seem to be as effective as radiation therapy for patients with choroidal metastases. In this paper a case of choroidal metastasis arising from a primary hypopharynx carcinoma is presented.

Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60–76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 ± 19% and 5-year actuarial survival was 24 ± 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile.

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m 2 for 1 day plus etoposide 120 mg/m 2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IlIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70–90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia ≥grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia >- grade 3 at nadir in seven cycles (9%). 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients ( P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

BACKGROUND The standard treatment for advanced (stage III and IV) head and neck squamous cell carcinoma (i.e., surgery with postoperative radiotherapy in operable patients and radiotherapy alone in inoperable patients) has had poor results. A series of randomized trials of induction chemotherapy have up to now failed to demonstrate an improvement in survival. PURPOSE This trial was designed to determine whether intensive induction chemotherapy administered before loco-regional treatment would improve survival of patients with advanced disease. METHODS Patients had previously untreated, advanced nonmetastatic (stages III and IV) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and paranasal sinuses. The study design was a randomized, multi-institutional, phase III trial. Eligible patients (n = 237) were randomly assigned to receive either initial chemotherapy (cisplatin and infusional fluorouracil) followed by loco-regional treatment (group A, n = 118) or loco-regional treatment alone (group B, n = 119). For operable patients (group A, n = 34; group B, n = 32), loco-regional treatment included resection followed by adjuvant radiotherapy. For inoperable patients, radical irradiation was performed with a planned dose of 65-70 Gy to involved areas. A dose of 45-50 Gy was also planned to the uninvolved neck or postoperatively. The statistical (log-rank) test was performed no earlier than 2 years after the randomization of the last patient. RESULTS Seventy-one patients (60%) in group A and 67 patients (56%) in group B were considered free of disease after they completed the treatment sequence. The analysis of time to distant metastases showed an advantage for group A patients. (Respective 2- and 3-year values for inoperable patients were 15% and 24% for group A versus 36% and 42% for group B, P = .04; only one operable group A patient had distant metastases after 49 months versus 26% [2 years] and 31% [3 years] for operable group B patients, P = .01.) For inoperable patients, the combined treatment was significantly associated with an increase in complete remission rate (group A, 44%) as compared with radiotherapy alone (group B, 30%) (P = .037). Inoperable patients also benefitted from induction chemotherapy in terms of disease-free survival (49% and 34% for group A versus 28% and 26% for group B; P = .06) and of overall survival (30% and 24% for group A versus 19% and 10% for group B; P = .04). CONCLUSIONS When all 237 randomly assigned patients were analyzed, there were no significant differences in the two treatment strategies in loco-regional failure or in disease-free or overall survival, although the development of distant metastases was reduced. For operable patients, the only benefit from neoadjuvant chemotherapy was a significant reduction in the incidence of distant metastases. For inoperable patients, neoadjuvant chemotherapy improved local control, decreased the incidence of distant metastases, and improved the complete remission rate and overall survival. IMPLICATIONS Confirmatory studies with effective chemotherapy regimens delivered for an adequate number of cycles are required.

e15591 Background: The prognosis of CC is related to both primary tumor stage, size, and histologic grade and to the lymph nodes status. Recently, the use of PET in CC staging is increasing. Furthe...

e16081 Background: C and G have synergistic activity when used in combination and are both potent radiosensitizers. In a dose finding trial, conducted in our hospital on ITBC patients using C and G with concurrent XRT, after maximum transurethral resection (TUR), the maximum tolerated dose of G was 400 mg/sqm (IJROBP 2003). On this basis, we have designed a phase II trial, which was prematurely closed, due to low accrual. We are presenting the long-term clinical outcome of the 16 patients involved in the dose-finding trial, together with that of the 9 pts enrolled in the phase II study. Methods: From June 1999 to December 2004, we have treated in our institution a consecutive series of 25 T2–4 N0 ITBC pts (median age 67 yrs, range 51–80). After macroscopically radical TUR, all pts received XRT (54 Gy in 30 fractions over 6 weeks) and concurrent C (100 mg/sqm, days 1, 22). In dose finding study G was given weekly from 200 to 500 mg/sqm: since unacceptable toxicity was observed in 2 cases (one death for toxicity) at the higher dose level, the recommended G dose for phase II trial was 400 mg/sqm on day 1,8 q 21 for 2 courses together with C and XRT. A cystoscopic re-evaluation was scheduled 6–8 weeks after treatment. Results: Except the pt died during treatment for toxicity, all the remaining 24 pts were microscopically disease free at cystoscopic re-evaluation. Seven local and 2 distant relapses have been observed so far, at a median follow-up of 66 mos. Presently, 16 pts (67%) is alive and disease-free, with 1 patient died for lung cancer. All pts alive have retained their bladder, with a normal organ function, in absence of any relevant long-term toxicity. The median survival has not been reached yet, while the OS at 7 years is 66%. The 5-year DFS, local DFS and survival without cystectomy, were 62%, 70%, and 95%, respectively. Conclusions: In our experience G + C with concurrent XRT in ITBC pts, appears encouraging, even at a long-term follow-up. Considering the 100% of complete response observed, this combination could be of interest to explore a possible enhancement of the disease control of C plus XRT, that is today the treatment of choice in the conservative therapy of ITBC. No significant financial relationships to disclose.

Photodynamic therapy (PDT) with porphyrins and red light is receiving increasing attention in the management of malignant tumours. At present PDT is primarily indicated for the treatment of superficial or early-stage lesions. At the Department of Radiotherapy and the First Institute of Surgery in Padova (Italy) more than 150 cases of tumours of different types have been treated using this technique. This paper briefly describes 21 cases of superficial oesophageal cancer. A complete response was observed in 11 of 21 cases. Radiation therapy appeared to be very effective as a salvage treatment of non-response patients.

Aims and backgroundMajor salivary gland cancers are rare, with many histologic types and subtypes. The low incidence and heterogeneity of primary parotid carcinomas makes their outcome difficult to evaluate. Treatment remains primarily surgical, but optimal therapeutic regimens have yet to be fully realized. The present study reviews the experience of three Italian institutions in the treatment of primary parotid carcinomas in order to describe the clinicopathological presentation and treatment options with emphasis on radiotherapy and to analyze the factors influencing survival.Methods and study designThe records of 110 patients with primary parotid neoplastic lesions treated at three Italian institutions from 1993 to 2004 were retrospectively reviewed. Six patients were excluded from the study: 3 received surgery alone and 3 were not assessable, for a total of 104 assessable patients. Acute and late toxicity of radiotherapy was quantified following the recommendations of the RTOG/EORTC. Survival was analyzed by the actuarial Kaplan-Meier product-limit method. The influence of selected factors on 10-year disease-specific survival was analyzed.ResultsThe 104 assessable patients were treated as follows: 11 patients received radiotherapy as their only treatment (3 with a palliative purpose) and 93 had postoperative radiotherapy. Thirty-two patients underwent neck dissection: neck lymph node metastases were found in all them. Their mean age was 60 years (range, 14–92). According to the UICC/2002 TNM Classification, 8 patients were stage I, 19 stage II, 34 stage III, 25 stage IVA, 5 stage IVB, 3 recurrent and 10 not assessable (Tx). The most frequent histologies were adenoid cystic carcinoma (n = 16), mucoepidermoid carcinoma (n = 15), and acinic cell carcinoma (n = 15). Twenty-three patients had recurrences: 10 had local recurrences, 3 neck recurrences, 9 distant metastases, and 1 patient had both local recurrence and distant metastases. No factors were observed that would negatively influence the prognosis. Actuarial 10-year disease-specific survival was 71% and actuarial 10-year local control 82%.ConclusionsThe treatment of salivary gland malignancies remains primarily surgical. Our study confirms the results of the literature with surgery and adjunctive radiotherapy in patients with advanced-stage disease. No variables were observed to influence the prognosis.

5532 Background: In 1986, the Gruppo di Studio sui Tumori Testa e Collo (GSTTC) started a multicenter randomized trial comparing induction CT with Cisplatin and 5Fluorouracil 120h c.i. (PF) followed by locoregional treatment (Surgery+RT or RT alone) (Group A) versus locoregional therapy (LRT) alone (Group B) in resectable or unresectable stage III-IVM0 H&N Squamous Cell Carcinoma. Our previous report (J Natl Cancer Inst 86: 265–72,1994), showed that 4 cycles of PF before LRT improved local control, decreased the incidence of distant metastases and increased Disease-Free-Survival (DFS) and Overall Survival (OS) in the subgroup of inoperable patients. Methods: From March 1986 to February 1990, 237 patients with stage III-IVM0 were randomized to 4 neoadjuvant PF followed by LRT or LRT alone. After a minimum follow-up of 10 years, the two treatments were compared in univariate and multivariate analysis for OS. Results: Of the 237 patients, 118 group A and 119 group B, 92% and 90% respectively were male, 25% a...

Aim to analyze the treatment outcome for E.P. (i.e. older than 70 yrs) affected by SCLC treated at our institution with the same protocol and entry criteria as younger pts. Results From 1980 to 1988, 286 patients (M/F 262/24) were treated; 254 (88%) were younger than 70 (Y.P.) while 32 (12%) were E.P., Pt. characteristics were similar in both age groups: median PS was 80% vs 80%, increased LDH 46% vs 47%, weight loss 55% vs 53%, limited disease (LD) stage 58% vs 56%. stages I-II 18% vs 18%, IIIA 26% vs 31%, IIIB 17.3% vs 15.6%, IV 38.2% vs 34.4%, operable pts 35% vs 31% respectively in Y.P. and E.P. Surgery, however, was performed in 73 (28.7%) Y.P. and in only 6 (18.8%) E.P. Chemotherapy (CT) consisted of 6 courses of alternating CAV/PE for extensive disease pts. LD pts were treated with 4 cycles of CT plus surgery in operable pts; RT (44 Gy) followed CT in inoperable pts. Two pts had an early death before starting treatment, 3 pts were submitted only to surgery fur refusal of CT, all in Y.P. group. In 44 pts surgery was followed by adjuvant CT. A total of 237 pts were submitted to primary CT, 210 pts were Y.P., 27 E.P.: objective response rates were 72% and 63% respectively, with 26.7% (56 pts.) and 22.2% (6 pts.) CR. Median survival was 11.6 and 12 months and 3 yrs survivals were 18% and 17.8%. Cox proportional hazard survival analysis showed no significant differences by age. Conclusions compliance, responses and survival were similar in Y.P. and E.P. treated for SCLC. Thus an aggressive therapeutical approach seems to be justified in selected patients older than 70 yrs.