False recalls, but not false recognitions, at the DRM paradigm are increased in subjects reporting insomnia symptoms: An online study.

BACKGROUND: In insomnia, poor sleep is accompanied by several cognitive impairments affecting prefrontal functioning that could affect source-monitoring processes and contribute to false memories production. By using a modified version of the Deese-Roediger-McDermott paradigm (DRM), we previously found that individuals suffering from insomnia produced more false memories than good sleepers adopting a free-recall task, especially for sleep-related stimuli. However, whether poor sleep affects false memory production in a task-dependent manner (i.e., free recall or recognition) remains unclear. METHODS: Through an online research method, we adopted the classical DRM paradigm to investigate the production of false recalls and false recognitions in 32 subjects referring insomnia symptoms (IN group) and 37 good sleepers (GS group), addressing also executive functioning and source monitoring ability in both groups. RESULTS: Compared to the GS group, the IN group produced more false memories (p = .002) and intrusions (p = .004) at the free recall task and showed a lower working memory index (p = .008). No between-groups differences emerged at the recognition task. Correlational analysis revealed significant associations between DRM performance, executive functioning and source monitoring (SM) variables. Moreover, false recalls were predicted by being in the presence of insomnia symptoms (p = .012) and intrusions by the number of correct responses to the Stroop task (p = .051) and SM task (p = .015), as well as by the presence of insomnia symptoms (p = .003). CONCLUSIONS: Our data show that the presence of insomnia symptoms can influence false memories production. Furthermore, the evidence that free recall is more affected than recognition suggests that poor sleep mainly affects performance at more cognitively demanding tasks. Finally, correlational and regression analyses support the hypothesis of a link between false memories production and both the presence of insomnia symptoms and executive functioning impairments.

Mammography before post-operative radiotherapy in conservatively managed breast cancer patients: is it useful?

OBJECTIVE: The aim of this study was to evaluate the role of bilateral mammography undertaken before adjuvant radiotherapy in patients with conservatively managed invasive carcinoma of the breast. METHODS: Patients with invasive breast cancer referred to the Radiotherapy Unit of the Università Cattolica del Sacro Cuore, in Campobasso, Italy, between March 2002 and September 2006 were retrospectively reviewed. Patients were referred to our facility from other local and regional hospitals where they received breast-conserving surgery and adjuvant chemotherapy. They presented to our department for post-operative whole-breast radiotherapy. All patients underwent physical examination and bilateral mammography prior to adjuvant irradiation. RESULTS: 201 patients met the selection criteria as delineated. Of these 201 patients who underwent pre-radiotherapy mammography, 3 had suspicious findings on mammography. In two of those cases, the histopathological examination confirmed the presence of residual disease within the residual mammary gland. In one case, the pre-radiotherapy mammogram allowed for the detection of disease persistence which was not otherwise appreciated on physical exam. In the other case, the diagnostic imaging confirmed only the findings of the physical exam. In both cases of residual disease, the tumour was found elsewhere in the breast and not at the primary site. In one patient, the radiological re-assessment led to a false-positive result. No cases of contralateral synchronous breast cancer were observed. The overall adjunctive cost of this strategy including a routine mammography besides the clinical visit was €7012 for all patients. CONCLUSIONS: No clear recommendation exists regarding post-operative mammography before adjuvant radiotherapy. In our experience, this strategy allowed for the detection of gross disease persistence after surgery which was not appreciated at clinical examination in 1 case out of 201. In this patient, adjuvant radiotherapy up to a total dose of 50 Gy would have been inadequate. Given the low cost of mammography, further investigation about its role in pre-radiotherapy evaluation is warranted.

Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery.

OBJECTIVE: Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases. METHODS: Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters. RESULTS: Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4. CONCLUSION: Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

Recurrent uterine cancer after surgery: magnetic resonance imaging patterns and their changes after concomitant chemoradiation.

PURPOSE: Our primary objective was to describe the magnetic resonance (MR) imaging patterns of recurrent uterine cancer after surgery and their changes following concurrent chemoradiation. The secondary objective was to identify MR imaging predictors of outcome. MATERIALS AND METHODS: Twenty-two consecutive women with biopsy-proven recurrent uterine cancer after surgery (cervix 13 patients, endometrium nine patients) were enrolled in this prospective study. Inclusion criteria were MR imaging at diagnosis and during follow-up and eligibility for concurrent chemoradiation. MR images were assessed for signal intensity of the pelvic relapse on T2-weighted images, site of relapse and infiltration of adjacent organs. Pre- and posttreatment MR images were compared on the basis of the same criteria. The 3D volume of relapses after treatment was calculated, and tumour response to treatment was evaluated as complete, partial, no change or disease progression. RESULTS: Recurrences appeared hyperintense on T2-weighted images in 22/22 (100%) patients. Pelvic relapse site was vagina in 5/22 (23%), vaginal vault in 9/22 (41%), vaginal vault with extension to the pelvic wall in 5/22 (23%) and pelvic wall in 3/22 (13%). Infiltration of adjacent organs was detected in 9/22 (41%) patients. The mean volume of recurrences on pretreatment MR images was 38.83 cm(3). On posttreatment MR images, relapses appeared hypointense in 19/22 (86%) patients and hyperintense in 3/22 (14%). The mean volume of recurrences on posttreatment MR images was 18.01 cm(3). Complete response was seen in 11/22 (50%) patients, partial response in 8/22 (36%) and no change in 3/22 (14%). CONCLUSIONS: MR imaging can provide an evaluation of all parameters necessary for planning treatment and assessing response to treatment.

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.

Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: safety, outcome, and prognostic measures.

OBJECTIVES: To evaluate the morbidity, and the therapeutic value of surgery after chemoradiation in a large series of locally advanced cervical cancers (LACC). The prognostic role of different clinico-pathological factors has been also evaluated. METHODS: Between October 1997 and October 2006, 161 LACC patients were treated at both the Gynecologic Oncology Units of the Catholic University of Rome and Campobasso. Radiotherapy was administered to the whole pelvic region in combination with cisplatin and 5-fluorouracil. Radical surgery was performed 5-6 weeks after the end of the treatment. RESULTS: A clinical complete/partial response was observed in 153 patients and radical surgery was performed in 152 cases. The overall rate of surgical complications was 33% with 15 (10%) patients experiencing severe toxicities. At pathological examination 111 of 152 patients (73%) showed absent/microscopic residual disease. With a median follow-up of 28 months, the 5-year disease free-survival (DFS) was 83% and the 5-year overall survival (OS) 90%. Advanced FIGO (Federation Internationale de Gynecolgie et d'Obstetrique) stage, pathological response and lymph node involvement were found significantly associated with clinical outcome. CONCLUSIONS: We confirmed in a larger series the safety and efficacy of this multimodal approach in the treatment of LACC. The pathological assessment of response can allow not only a tailored surgery in selected patients, but also the identification of patients with higher risk of recurrence to be submitted to adjuvant therapies.

Intraluminal brachytherapy without stenting in intrahepatic papillary cholangiocarcinoma: a case report.

A 46-year-old female patient, with mild cholestasis by a large papillary cholangiocarcinoma involving the left hepatic duct, received intraluminal brachytherapy (50 Gy at 1 cm from the source axis) with the aim to relieve biliary obstruction without stent positioning. The patient presented with haemobilia and vegetant lesions in the left main biliary duct, and thus she had a high risk of early stent obstruction. Eighteen months after the treatment the patient presented tumour progression in the controlateral hepatic lobe, but had a patent left hepatic duct, without signs of cholestasis and/or cholangitis. Based on this and other published reports, intraluminal brachytherapy may be tested in a setting different from standard setting with the aim to safely palliate jaundice in patients with intraductal tumour growth in the biliary tract.

Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging.

BACKGROUND: To report the efficacy of induction treatment (IT) protocol with concurrent radiochemotherapy in locally advanced non-small-cell lung cancer (NSCLC), and to analyze downstaging as a surrogate end point. PATIENTS AND METHODS: Patients with histo- or cytologically confirmed stage IIIA or IIIB NSCLC were treated according to an IT protocol followed by surgery. Downstaging was assessed for all resected patients. RESULTS: In the period between February 1992 and July 2000, 92 patients were enrolled in the study (57 IIIA, 35 IIIB). Response was observed in 63 patients; 56 patients underwent radical resection. Patients downstaged to stage 0-I (DS 0-I) showed a statistically significant improved disease-free survival (26.2 months pStage 0-I versus 11.2 months pStage II-III; P=0.0116) and overall survival (median 32.5 months pStage 0-I versus 18.3 months pStage II-III; P=0.025). Patients with DS 0-I had a significantly lower probability (P=0.0353) of developing distant metastases estimated in 0.2963 odds ratio. CONCLUSION: Neoadjuvant radiochemotherapy is feasible with good pathological DS results. Pathological downstaging was confirmed to have high predictive value. Its use is suggested in the short-term evaluation of induction protocols efficacy in locally advanced NSCLC.

Concomitant gemcitabine (Gemzar) and extended nodes irradiation in the treatment of pancreatic and biliary carcinoma: a phase I study.

BACKGROUND: The rationale for combining cytotoxic agents, such as gemcitabine, and radiotherapy is based on their ability to act as radiation sensitizers and to improve overall response rate. Several studies on pancreatic or biliary carcinoma evaluated the maximum tolerated dose (MTD) of gemcitabine when combined with irradiation of the macroscopic tumor. However, most of these neoplasms metastasize to the regional lymph nodes. Aim of this report is to determine the MTD of weekly gemcitabine when combined with extended field irradiation (tumor plus nodal irradiation). PATIENTS AND METHOD: 15 patients entered the study. Of these 5 patients were treated with chemoradiation after radical surgical resection. External beam radiation (ERT) was delivered to the tumor (or tumor bed) and regional lymph nodes by using a three-field technique. The initial dose of gemcitabine was 100 mg/m(2) administered as short intravenous infusion once a week. At each dose level 3 patients were treated, and if no grade 3-4 toxicity (considered as dose-limiting toxicity, DLT) was recorded, dose escalation was applied with 50 mg/m(2) increments until the MTD was established. RESULTS: All patients were evaluable for acute toxicity. There were no treatment-related deaths. No DLT occurred at the first 4 dose levels (100-250 mg/m(2)). At the 5th dose level (300 mg/m(2)), 3 patients experienced DLT: 1 had grade 3 gastrointestinal toxicity (painful erosion of gastric mucosa), 1 had uncomplicated grade 3 leukopenia and 1 grade 3 change in liver biochemistry tests. In addition, all 10 unresected patients were evaluated for response, 4 of whom had progressive disease (1 local; 2 distant; 1 local and distant) and 6 had no change. The median follow-up was 21 months. CONCLUSION: Based on this study, the recommended dose for weekly short infusional gemcitabine combined with radiation therapy to the tumor and lymph nodes is 250 mg/m(2). This value is suggestive of a correlation between acute toxicity and inclusion of lymph nodes in the irradiated volume. Moreover, different infusion modalities, as continuous infusion gemcitabine, should be tested more accurately.

Locoregional pain treatment. Troubles and prospectives: antalgic radiotherapy.

Pain control in patients with cancer represents a significant aspect of radiation therapy practice. Radiation therapy is one of the most effective, and often the only, therapeutic option to relieve pain caused by nerve compression or infiltration by malignant tumor, pain from liver and bony metastases and it provides also successful palliation of dysphagia caused by oesophageal carcinoma and of pain due to pancreatic cancer. Various instruments are avaliable for pain evaluation but a valid methodology to assess the pain status in the patient with cronic cancer pain is still an important clinical problem. In this complex and wide scene this contribution wants to confirm the role of radiotherapy in cancer pain control, in paricular in bone metastases, and to involve the patient himself in the survey of radiation treatement response by a subjective evaluation of bone pain, elaborating a reliable and valid unidimensional method by which recording the self-rating of the patient's sensation. Materials and Methods For the subjective evaluation of pain caused by bone metastases we used an application form with which drawing information in the course of time in terms of: response to the treatment, duration of symptom relief and quality of life. Results Considering as cut-off a dose of 30 Gy, which is commonly considered the conventional treatment for bone metastases, the partial and complete response were, respectively, of 54% and 30% in the patients treated with dose higher than or equal to 30 Gy, and 60% and 20% in the ones treated with doses lower than 30 Gy. In the whole, in 84 patients, the global response was of 82%, in accordance with literature. Conclusion In this retrospective study, the analysis of patient's subjective experience confirmed the effectiveness of radiotherapy in reducing pain caused by bone metastases and in improving quality of life of the patient himself. Given the conflicting opinions on low-dose short-course radiotherapy versus prolonged or higher dose schedules on initial pain relief, we are going to define categories of homogenous patients on whom starting treatment schedules with the aim or of palliation of the symptom or of the functional restitutio, on the base of the expectation and the quality of life.

Adjuvant radiotherapy in resectable pancreatic carcinoma.

AIM: Pancreatic cancer is a near fatal disease. External beam radiotherapy and intraoperative radiation therapy (IORT) has been proposed with the aim to improve clinical outcome in resectable tumors. The aim of this study is to assess the feasibility and outcome in patients with cT1-3 pancreatic cancer, treated with surgery, external beam radiotherapy and IORT. METHODS: From 1990 to 1996, 17 patients with clinical stage T1-3N0-1M0 adenocarcinoma of the head of the pancreas were treated with pancreatectomy and pre- (nine patients: 5 Gy), intra- (all patients: 10 Gy) and post-operative (all patients: 50 Gy) radiotherapy. The pathologic T stages were: 4 pT2 and 13 pT3. The pathologic N stages were: 9 pN0 and 8 pN1. Minimum follow-up in living patients was 60 months. RESULTS: No perioperative mortalities were recorded. Two patients showed postoperative morbidity (11.8%) which required a subsequent laparotomy. The disease-free survival at 1, 3 and 5 years was 41, 23 and 18%, respectively (median: 9 months). The overall survival at 1, 3 and 5 years was 70%, 41% and 18%, respectively (median: 17.5 months). Three patients developed local failure (17.6%) and 12 patients showed distant metastases (70.6%). Univariate analysis (logrank) showed: a significant correlation between both N-stage and retroperitoneal involvement (RPI) with local control (N-stage: P=0.0155; RPI:P =0.0295), a significant correlation between maximum tumor size and metastases-free survival (P=0.0167) and overall survival (P=0.0241); the female gender was another predictor of prolonged survival (P= 0.0465). Multivariate analysis (Cox) showed a significant impact of N-stage and retroperitoneal involvement on local control and also a significant correlation between perineural involvement and tumor diameter with metastases-free survival. CONCLUSIONS: These results are similar to those of other published series and suggest that this approach is feasible with acceptable local control and survival, especially in patients with small tumors (<2.5 cm: 5 year survival=33.3%) and in female patients (5 year survival=30%). Due to the impact of gender, tumor diameter and N stage on prognosis, in the design of future trials a stratification of patients based on these categories should be considered. The search of effective chemotherapeutic agents is required, to reduce the high incidence of distant metastases, especially in larger tumors.

Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study.

The use of raltitrexed ('Tomudex') as concomitant chemotherapy during preoperative radiotherapy in chemonaïve patients with stage II/III rectal cancer has been examined in this study and its recommended dose in conjunction with radiotherapy investigated. Forty-five Gray (Gy) of radiotherapy (1.8 Gy daily, 5 days per week) was delivered to the posterior pelvis, followed by a 5.4 Gy boost. Single doses of raltitrexed (2.0, 2.5 and 3.0 mg/m(2)) were administered on days 1, 19 and 38. Only 1 of the 15 patients entered experienced a dose limiting toxicity (DLT) (grade 3 leucopenia) at the 3.0 mg/m(2) dose level. The overall response rate was 80% (five complete responses, seven partial responses). These preliminary data suggest that raltitrexed is a well tolerated and effective treatment when combined with preoperative radiotherapy in patients with stage II/III rectal cancer. The recommended dose of raltitrexed for future phase II studies will be 3.0 mg/m(2).

Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies.

PURPOSE: To compare acute toxicity, tumor response, and sphincter preservation in three schedules of concurrent chemoradiation in resectable transmural and/or node-positive extraperitoneal rectal cancer. PATIENTS AND METHODS: Between 1990 and 1999, 163 consecutive patients were treated according to the following combined modalities: FUMIR: between 1990 and 1995, 83 patients were treated with bolus i.v. mitomycin C (MMC), 10 mg/m(2) day 1, plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1,000 mg/m(2) days 1-4, and concurrent external beam radiotherapy (37.8 Gy). PLAFUR-4: between 1995 and 1998, 40 patients were treated with cisplatin (c-DDP) 60 mg/m(2) given as slow infusion (1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-4 and 29-32 with concurrent external-beam radiotherapy (50.4 Gy). PLAFUR-5: between 1998 and 1999, 40 patients were treated with c-DDP 60 mg/m(2) given as slow infusion (during 1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-5 and 29-33 with concurrent external-beam radiotherapy (50.4 Gy). RESULTS: Grade > or = 3 acute toxicity occurred in 14%, 5%, and 17% of patients treated in the FUMIR, PLAFUR-4, and PLAFUR-5 studies, respectively (p = 0.201). In the FUMIR, PLAFUR-4, and PLAFUR-5 studies, clinical response rate was 77%, 70%, and 83%, respectively. Tumor downstaging occurred in 57%, 68%, and 58% of patients, respectively. Pathologic complete response was recorded in 9% (FUMIR), 23% (PLAFUR-4), and 20% (PLAFUR-5) of patients. Sphincter-preserving surgery was feasible in 44% (FUMIR), 40% (PLAFUR-4), and 61% (PLAFUR-5) of patients having a distance between the anal-rectal ring and the lower pole of the tumor of 0-30 mm, and in 95%, 100%, and 100%, respectively, in those having a distance of 31-50 mm. Comparing FUMIR vs. PLAFUR, the clinical response rate was similar in the two series: a partial response was observed in 62/81 (77%) patients with FUMIR treatment, and in 61/80 (76%) patients with PLAFUR treatment. Tumor downstaging was observed in 46/81 (57%) patients and in 50/80 (68%) patients, respectively. The pathologic complete response rate was statistically higher in the PLAFUR series: 7/81 (9%) patients with FUMIR treatment and 17/80 (21%) patients with PLAFUR treatment (p = 0.04). Major downstaging (pT0+ pTmic+ pT1) in the FUMIR group was reported in 12/81 (15%) patients versus 31/80 (39%) patients in the PLAFUR group (p = 0.0006). The anal sphincter was preserved in 63/81 (78%) patients with FUMIR treatment and in 69/80 (86%) patients with PLAFUR treatment. The perioperative morbidity was statistically lower with PLAFUR: a perioperative morbidity was experienced by 20/81 (25%) patients with FUMIR treatment and by 9/80 (11%) patients with PLAFUR treatment (p = 0.042). CONCLUSION: In our experience, higher radiation dose (50.4 Gy vs. 37.8 Gy), a second course of concurrent 5-FU, and the use of c-DDP instead of MMC improved the pathologic response rate without increasing acute toxicity and perioperative morbidity. The use of 5-FU 5-day infusion (PLAFUR-5) resulted in higher toxicity with a similar response rate compared to 4-day infusion (PLAFUR-4).

A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.

BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02). There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

Improved survival and local control after intraoperative radiation therapy and postoperative radiotherapy: a multivariate analysis of 46 patients undergoing surgery for pancreatic head cancer.

HYPOTHESIS: Despite aggressive approaches, locoregional tumor control and survival rates for patients with cancer of the pancreatic head remain disappointing. In the present study, we address whether intraoperative and adjuvant radiotherapy may improve the prognosis for these patients. DESIGN: A retrospective study. SETTING: University hospital. PATIENTS: From February 1985 to December 1995, 46 patients with an adenocarcinoma of the pancreatic head underwent pancreatic resection. The last 26 patients also received intraoperative radiotherapy (except 5 patients) and adjuvant external beam radiation therapy. MAIN OUTCOME MEASURES: Demographic data, tumor characteristics, surgical procedures, 5-year survival, and local control of disease were analyzed retrospectively. RESULTS: The morbidity rate was not increased by adjuvant radiation therapy; it was 43% in patients treated with surgery alone and 57% in patients treated with surgery and radiotherapy (P =.1); operative mortality was 8% (n = 2) and 9% (n = 2), respectively (P =.8). Overall 5-year survival and local control were 13% and 48.6%, respectively. The mean +/- SD 5-year survival was 5.5% +/- 5.3% (median, 10.8 months) in the surgery-alone group and 15.7% +/- 8.6% (median, 14.3 months) in the surgery plus radiotherapy group (P =.06); local control at 5 years was 29.8% +/- 16.9% and 58.4% +/- 19.9%, respectively (P<.01). Median metastasis-free survival was 8 and 9 months, respectively (P =.52). Multivariate analysis showed that adjuvant radiotherapy was an independent prognostic factor for survival (P<.01) and local control of the disease (P =.03). CONCLUSION: The present study supports the role of radiotherapy combined with pancreatoduodenectomy for treatment of cancer of the pancreatic head because even if the improvement in overall survival is moderate, it is effective in improving the local control of the tumor.

Quality handbook in radiotherapy: personal experience.

The Quality Handbook includes the description of the activities carried out in Radiotherapy and the methodology used to ensure the Quality Assurance according to the principles indicated in national and international documents of reference and the recommendations of accreditation agencies. The structure of the Quality Handbook, the main aspects of single chapters, the selected quality indicators undergoing inspections are analysed and procedures to be followed for changes and updating of the Quality Handbook are described. The Quality Assurance program is illustrated in another article of this issue.

Quality handbook in radiotherapy. Brachytherapy: personal experience.

Brachytherapy is a conventional method of radiation therapy characterized by peculiar technical, clinical, operational and radioprotection problems. Therefore, the management of a service or department of brachytherapy requires a specific organization aimed at Quality Assurance. In this report, the personal experience with the drawing up of a Quality Handbook of brachytherapy with reference to the method used and the structure of the document, is described.

Quality assurance in radiotherapy: personal experience.

The approach to the implementation of a Quality Assurance Program applied from 1 October 2000 at the Radiotherapy Service of the "Università Cattolica del S. Cuore, Policlinico "A. Gemelli" of Rome, is described. Some major aspects of this program are analyzed.

[Simultaneous radiochemotherapy in rectal tumors]. / La radiochemioterapia concomitante nei tumori del retto.

After about 30 years from the first trials on concurrent chemoradiation in the treatment of rectal carcinoma, a large experience in this field has been shared, both in terms of laboratory and clinical data. The possibility of concurrent chemoradiation to improve the clinical outcome and sphincter preservation in low rectal tumors has been extensively demonstrated. Great attention should be paid to the quality of radiation treatment and drug administration, to minimize the risk of therapy-related toxicity. The impact of preoperative chemoradiation on tumor control will be further clarified by the ongoing randomized studies, in terms of comparison with radiation therapy alone (EORTC study), "Total mesorectal excision" (Duch Study), postoperative chemoradiation (German CAO/ARO/AIO 94) and the potential role of adjuvant chemotherapy (EORTC and Italian study). A series of phase II studies will probably clarify the role of unconventional fractionation modalities (hyperfractionation, accelerated treatments) and of new concomitant chemotherapy (new drugs, chronomodulation) in terms of organ and sphincter preservation. A close cooperation between radiation oncologists, medical oncologists and surgeons is required.

Phase I-II trial of preoperative chemoradiation in locally advanced cervical carcinoma.

BACKGROUND: 5-Fluorouracil and cisplatin are characterized by in vitro synergism as well as radiosensitization. A phase I-II study was carried out on patients with invasive cervical carcinoma (FIGO IIB-IIIA) undergoing concomitant chemoradiation with 5-fluorouracil and cisplatin followed by radical surgery. METHODS: Twenty-six patients of 53 years median age, 24 with IIB tumor and 2 with IIIA tumor, all with squamous carcinoma, entered the study. The chemoradiation protocol included external radiotherapy to the pelvis: 39.6 Gy (180 cGy/daily); 5-fluorouracil: 1 g/m(2)/daily, in continuous intravenous infusion days 1-4 and 27-30; cisplatin: 20 mg/m(2)/daily days 1-4 and 27-30. Four weeks after the end of chemoradiotherapy, patients underwent restaging and then radical surgery with pelvic and lumboaortic lymphadenectomy. RESULTS: Twenty-six patients are evaluable for acute toxicity and 24 are evaluable for objective and pathologic response. Grade 3-4 thrombocytopenia or leukopenia was observed in 6 patients and grade 3 acute gastrointestinal toxicity in 3. After chemoradiation CR and PR were observed in 64 and 36% of cases, respectively (CR + PR = 100%). Two patients were excluded from surgery for other diseases. The remaining 24 patients were operated on; 23/24 patients showed negative section margins. The histology of the surgical specimen showed the absence of disease in 13 patients (54.2%), microscopic residual tumor in 4 patients (16.6%), residual disease 1 cm in 2 patients. Median follow up was 33 months. Two-year actuarial local control was 91.7%. CONCLUSIONS: This study showed a particularly high rate of pathologic responses (complete + Tmic: 70.8%) and local control (2 years = 91.7%) in patients with advanced cervical cancer undergoing moderate doses of radiotherapy with concomitant chemotherapy followed by radical surgery.