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Intraoperative radiotherapy is a feasible technical modality to improve precision and dose-escalation in high-local risk lung cancer patients. Methodology is described regarding the use of high-energy electron beams or brachytherapy. Results of normal tissue tolerance in experimental animal models and in clinical experiences are analyzed in detail. Characteristics of clinical experiences using IORT electrons or brachytherapy are reported and clinical outcome results are discussed. Ten IORT brachytherapy and six electron-based publications are identified proving the adaptability of IORT to the clinical-therapeutic scenario of lung cancer, its feasibility and the promotion of high local control rates in the context of dose-escalation trials.

Management of soft-tissue sarcomas of the extremities and trunk is optimally accomplished through a multidisciplinary team evaluation of each patient because of the diverse and complex nature of each clinical scenario. A team of orthopedic or surgical oncologists, radiation oncologists, medical oncologists, plastic surgeons, pathologists, and radiologists consider multiple issues including tumor stage, grade, location, and histologic type of tumor, as well as feasibility of a limb-sparing surgery, timing of radiation, and the patient’s performance status and comorbid illnesses. The rarity of these tumors in combination with the variety of presentation in extremity and truncal soft-tissue sarcomas limits the amount of prospective data available to reliably outline the management of all situations, and hence, there is a range of approaches utilized around the world today.

A retrospective analysis to assess the feasibility and clinical tolerance of intraoperative radiotherapy (IORT) in the treatment of recurrent gynecologic cancer is reported. From February 1985 to September 1992, 26 patients with recurrent gynecologic tumors entered this trial. The clinical experience comprises two different categories of disease situations: tumors relapsing after full dose radiation therapy (group I) and recurrent disease to previous surgery (group II). Cervical carcinoma was the initial tumor site of involvement in 18 patients (69%). Treatment consisted in maximal surgical resection + IORT boost (10–25 Gy) to the high-risk areas for recurrence. Non previously irradiated patients also received external beam irradiation (EBRT) (± chemotherapy) preor postoperatively. IORT-related toxicity was one episode of motor neuropathy. Local control rates have been 33% and 77%, respectively in groups I and II. The 4-year actuarial overall survival in Group I is 7% and 6-year actuarial overall survival in Group II is 33%. The addition of IORT to surgical debulking achieves modest local control and long-term survival rates if tumor-free margins cannot be obtained in previously irradiated patients. Combined EBRT (± chemotherapy) maximal surgical resection plus IORT could render some long-term survivors among those surgical recurrent patients not candidates for radical surgery with curative intent.

Absence of residual cancer (pT0) in the cystectomy specimen was evaluated in patients with invasive bladder cancer treated with intraoperative (IORT) (15 Gy) and preoperative external beam radiotherapy (EBR) (46 Gy/5 weeks) with or without neoadjuvant chemotherapy. The overall pT0 rate was 68% (67% and 70% in patients with or without neoadjuvant chemotherapy, respectively). The tolerance to the program was acceptable in both groups. It is concluded that intense, combined modality treatment is feasible in bladder cancer patients, and the addition of neoadjuvant chemotherapy does not increase the morbidity. Preliminary results on disease-free survival are encouraging.

Background: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). Patients and methods: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo) radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. Results: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. Conclusions: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Summary Background Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15–27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. Methods In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. Findings 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0–277). 5-year crude disease-free survival was 83·3% (95% CI 78·8–87·0) for patients with pCR (61/419 patients had disease recurrence) and 65·6% (63·6–68·0) for those without pCR (747/2263; HR 0·44, 95% CI 0·34–0·57; p Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0·54 (95% CI 0·40–0·73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0·91 (95% CI 0·73–1·12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Interpretation Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. Funding None.

BACKGROUND AND METHODS Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year. RESULTS In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient. CONCLUSIONS These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.

Thirty patients with malignant tumours in the upper abdomen underwent surgery and intraoperalive radiation (IORT), using electron beam, to: the surgical bed, residual or unresected tumour. The technical aspects and results of this treatment are described. Renal, adrenal, bile duct and gastrointestinal tumours were treated. along with several other lesions. The surgical procedure consisted in 10 cases simply of exposure of the tumour for IORT and in 20 the tumour was resected. The TORT dose ranged from 10 to: 20 Gv. In 13 patients, external beam radiation was also given to: residual tumour or to: areas of high risk for recurrence. Chemotherapy was given to: 10 patients. Tolerance to: the combined treatment was acceptable; with few complications related to: IORT.

Intestinal hemorrhage due to arteriodigestive fistula is described to be a rare and serious complication of radiotherapy. Three cases of this type of fistula in gastric cancer patients treated with gastrectomy, intraoperative electron boost (15 Gy), and fractionated external beam irradiation (46 Gy) are reported. Selective angiography is most helpful in the diagnosis and immediate surgery could be lifesaving. An attempt to explain the etiopathogenesis is made.

From September 1984 to August 1991, 48 evaluable patients with resected gastric cancer and apparent disease confined to locoregional area were treated with intraoperative electron beam boost to the celiac axis and peripancreatic nodal areas (15 Gy) and external irradiation (40 to 46 Gy in 4 to 5 weeks) including the gastric bed and upper abdominal nodal draining regions. At the time of evaluation for IORT, the disease was primary in 38 cases, recurrent but resectable in four (anastomosis), and unresectable in four (nodal). Post operative complications were reversible. Acute tolerance to the complete treatment program was acceptable. Late complications included life-threatening events: Six episodes of gastro intestinal bleeding (three of them had an arteriographic documentation of arterioenteric fistula) and nine with severe enteritis (five required reoperation). Other long-term treatment related complications were six cases of vertebral collapse. The median follow-up time for the entire group is 22 months. Locoregional recurrence/persistence of disease has been identified in five patients (three with residual and/or recurrent postsurgical tumor). Systemic tumor progression has been detected in 15 patients (11 in intra-abdominal sites). Overall actuarial survival for patients with positive or negative serosal involvement was 33% versus 56%. It is concluded that the treatment program described is able to induce a high locoregional tumor control rate (100%) when used strictly in an adjuvant setting and might control long term, a small portion of patients not amenable for curative surgery (2 out of 8 patients with confirmed residual post-surgical disease). Gastrointestinal bleeding and enteritis are findings that indicate treatment intensity at the upper limits of tissue tolerance. Assessment of long term tolerance of pancreatic parenchyma and large blood vessels (tissues included in the IRORT field) are pending for longer follow-up and the appropriate selective studies.

Objective To evaluate efficacy of 18 F-FDG PET(CT) in the staging and re staging of patients with locally advanced rectal cancer, its potential role in predicting pathological response to neoadjuvant therapy. Patients and methods Patients with confirmed diagnosis of rectal cancer (T2–4 or N+) were prospectively studied with 18 F-FDG PET before and after neoadjuvant therapy. Surgery was programmed 4–6weeks after treatment followed by an expert histological analysis of the surgical specimen. Response to neoadjuvant treatment was assessed using two specific variables: difference in SUV (difSUV) pre/post-neoadjuvant treatment and response index (RI). Results A total of 64 patients were enrolled for pathological and bio-metabolic response assessment. Compared to cN0, cN+ patients had a higher SUV 1 mean value (6.5 vs. 7.6, p =0.04) and ypN+ patients had higher SUV 2 mean values (2.4 vs 3.5, p =0.06). difSUV values of ⩾4 was the most efficient diagnostic parameter (sensitivity=45.8%, specificity=86.2%, positive predictive value (PPV)=73.3%, negative predictive value(NPV)=65.7%). With an RI of 66.6%, the sensitivity was 38.5%, specificity=81.5%, PPV=66.6%, and NPV=57.8%. Patients who experienced disease progression had an RI⩽66% and a difSUV⩽4. Conclusion 18 F-FDG PET has proven to be an accurate diagnostic technique for assessing rectal cancer response to neoadjuvant therapy. The results in terms of sensitivity, specificity, PPV and NPV were similar, if not superior, to those reported with other diagnostic imaging techniques.

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisciplinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6-20 MeV electron beams. The median follow-up time for the entire group is 25 months (2-65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.

Purpose: A joint analysis of data from five contributing centers within the ISIORT-Europe program was performed to investigate the main contributions of intra-operative radiotherapy (IORT) to the multidisciplinary treatment of pancreatic cancer. Materials and methods: Patients with a histologic diagnosis of carcinoma of the pancreas, with an absence of distant metastases, undergoing surgery with radical intent and IORT were considered eligible for participation in this study. Results: From 1985 to 2006, a total of 270 patients were enrolled in the study from five European Institutions. Surgery was performed in 91.5% of cases and complicated by adverse events in 59 cases. External radiotherapy (ERT) preceded surgery in 23.9% of cases. One-hundred and six patients received further ERT. After surgery + IORT, median follow-up was 96 months (range 3-180). Median local control was 15 months, 5-year local control was 23.3%. Median overall survival was 19 months, while 5-year survival was 17.7%. A significantly greater local control and survival were observed in patients undergoing preoperative radiotherapy (LC: median not reached; OS: median 30 months) compared to patients treated with postoperative ERT alone (LC: median 28 months; OS: median 22 months), and to patients submitted to IORT exclusively (LC: median 8 months; OS: median 13 months) (p < 0.0001). Conclusion: From this joint analysis emerges the fact that preoperative radiotherapy increases the effects of IORT in terms of local control and overall survival. The 5-year local control of 23.3% confirms the beneficial "sterilizing" effect of IORT on the tumor bed. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 91 (2009) 54-59

A Phase I–II study of intraoperative radiotherapy (IORT) for Stage III lung cancer was performed in 34 patients during a period of 58 months. Loco-regional treatment included tumor resection if technically feasible, IORT boost of electron beams using moderate single doses (10–15 Gy) to tumor bearing areas and external photon beam irradiation (46–50 Gy in 5 weeks) using conventional fields. Indications for this study were unresectable hiliar tumors (14, 41%), and mediastinal, hiliar and/or chest wall residual disease following resection (20, 59%). Thirty-four procedures, with 40 IORT fields, have been analyzed to describe the relevant technical aspects and the toxicity. IORT was delivered using acrylic transparent cones of different diameters. Surgical approach consisted in a lateral thoracotomy in all patients (21 right side and 13 left side). Tissues included within the IORT field were: tumor or residual tumor tissues (34, 100%), collapsed lung parenchyma and main bronchus not surgically manipulated (14, 41%), bronchial stump and vascular suture following resection (19, 55%), mediastinal structures (20, 58%), and brachial plexus (1, 3%). The bronchial suture was covered with pleural or pericardial flap after IORT in 10 cases (29%). Life threatening toxicity related to IORT consisted in broncho-pleural fistula (1, 3%) and massive hemoptysis (1, 3%). Other reversible toxic events were acute pneumonitis (12, 85%) and esophagitis (10, 50%). Long term asymptomatic lung fibrosis was detected in 11 cases (32%). Median survival time for the entire group has been 12 months. With a median follow-up time of 12 months the freedom from thoracic recurrence rate is 30% (65% in cases with tumor resection). Projected actuarial survival rates at 4 years were 28% for resected group and 7% for unresected cases. This experience supports IORT as a feasible alternative modality to be used in the management of locally advanced lung cancer. Tolerance of thoracic organs to moderate doses of IORT appeared to be adequate and local control is achieved in certain patients. These results deserve further investigation and confirmation trials.

Recently it has been reported in the EORTC (European Organisation for Research and Treatment of Cancer) trial 22911 and the SWOG (Southwest Oncology Group) 8794, the evidence that radiotherapy (RT) is an effective treatment after the prostatectomy in patients with high risk of biochemical failure. We analyze predictor factors of biochemical relapse and the potential benefits induced by rescue treatment are the main purposes of our study.From 1993 to 2003, 597 prostatectomy were followed at Hospital Universitario Gregorio Marañón de Madrid, identifying 166 patients (p) (28%) of biochemical failure (defined as PSAor = 0'5 ng/ml, including post-surgical persistent values). 42 p received RT (78% due to delayed PSA relapse). The median total dose was 66 Gy [60-74].Clinical variables: Median age: 68 years [49-80], median PSA at diagnosis: 29,8 ng/ml [2,6475]; presurgical Gleasonor = 7: 65%. Histological variables: Prostatectomy induces stage migration to superior T (pT3-T4: 95%) and Gleason categories (or =7: 81%). 83% of relapsed p had positive margins and 90% had pT3-pT4.median time to biochemical recurrence was 22,2 months. Median time interval between biochemical failure and RT was 10,5 months. Overall survival (5 years) was 86 +/- 6%. Freedom-from-biochemical failure at 5 years was 76 +/- 4%. RT had poor survival in p with PSA2 ng/ml pre-RT (p = 0.03), post-prostatectomy persistant disease (p = 0.05) and Gleason scoreor = 7 (p = 0.01). No increased grade 3-4 uro-rectal toxicity was observed.RT after prostatectomy improves freedom-from-biochemical failure in p with PSA values below 2 ng/ml. In our experience, Gleason scoreor = 7 is a negative predictor of response. There is no severe toxicity in our series. Improvement of the staging presurgery, the role of the adjuvant androgen deprivation and selection of patients for adjuvant RT focus current studies on treatment after prostatectomy.

Objetivo: Recientemente se han comunicado firmes evidencias por la EORTC (European Organisation for Research and Treatment of Cancer - ensayo 22911) y el SWOG (Southwest Oncology Group - ensayo 8794), señalando que la radioterapia (RT) es un tratamiento eficaz tras la prostatectomía en pacientes con alto riesgo de fracaso bioquímico. Definir el momento óptimo para su administración e identificar factores de riesgo predictivos de recidiva, son objetivos transcendentes para guiar la práctica asistencial. Métodos: Desde 1993 hasta 2003, 597 pacientes fueron tratados con prostatectomía radical en el Hospital General Universitario Gregorio Marañón y áreas de referencia asistencial. 166 pacientes (28%) desarrollaron una recidiva bioquímica (definida como PSA ≥0,5 ng/ml e incluyendo aquellos casos con persistencia tumoral). Cuarenta y dos, recibieron tratamiento con RT (78% tras fallo bioquímico). La dosis media de RT fue de 66 Gy [60-74]. Resultados: Variables clínicas: Edad media: 68 años [49-80], media del PSA al diagnóstico: 29,8 ng/ml [2,6-475], Gleason prequirúrgico ≥7: 65%. Variables patológicas: Tras la prostatectomía, los pacientes tenían datos de mayor agresividad histológica que la definida previamente en las biopsias, apareciendo Gleason ≥7 en el 81% de los pacientes. El 83% a su vez tenían borde afecto y en el 90% de los casos el estadio era pT3-pT4. Variables evolutivas: El tiempo medio de aparición de la recidiva bioquímica fue de 22,2 meses, con un intervalo de 10,5 meses desde el diagnóstico hasta el inicio de la RT. La SG fue de 86±6 % a los 5 años y la Supervivencia Libre de Fracaso Bioquímico (SLFB) fue de 76±4% a los 5 años. Los factores predisponentes para la recidiva fueron: PSA 2 ng/ml al inicio de la RT (p=0,03), persistencia tumoral (p=0,05) y Gleason ≥7 tras la prostatectomía (p=0,01). No se observó un aumento de la toxicidad grado 3 y 4 en los pacientes tratados con RT. Conclusiones: La RT tras prostatectomía es un tratamiento eficaz de rescate tras recidiva bioquímica o persistencia cuando el PSA no supera los 2 ng/ml. En nuestra serie, el Gleason ≥7 es un factor adverso de respuesta a la RT de rescate. No existe un aumento de la toxicidad severa. La mejora de las técnicas de estadificación prequirúrgica, el papel de la hormonoterapia adyuvante y la selección de los pacientes para RT adyuvante centran los estudios actuales de los tratamientos tras prostatectomía.

Purpose/Objective(s): ACEi and ARB are commonly prescribed medications in the management of hypertension and diabetes. Pre-clinical and clinical data has suggested mitigating effects of these drugs on radiationinduced lung injury, which has implications for thoracic radiation therapy (RT). Whether ACEi/ARBs have a negative effect on tumor response still needs to be elucidated. In this study, we examined the correlation between ACEi/ARB and incidence of pCR as a surrogate for anti-tumor effect in patients receiving trimodality therapy for esophageal cancer. Materials/Methods: Between March 2000 and July 2012 135 patients with esophageal cancer were treated with NA-CRT followed by esophagectomy at our institution. The median age at diagnosis was 59 years (range, 26-82). The cohort was dominated by male patients (86%), distal esophageal primary (89%) and adenocarcinoma histology (76%). Predominant stage distribution was stage III (47%) and stage II (36%). Median radiation dose was 50.4 Gy (range 45.0-56.4Gy). Most common concurrent chemotherapy regimen was Cisplatin/5-Fu (59%). Primary endpoint was pCR rates with secondary endpoints of overall survival (OS) and progression free survival (PFS). Chi-square analysis along with univariate and multivariate Kaplan-Meier and Cox Regression analysis were performed. Results: With a median follow-up of 2.1 years, estimated median OS and PFS for the entire cohort were 2.7 years (95% CI: 2.0-3.4) and 2.8 years (95% CI: 1.9-3.7). 45 patients (33%) were taking ACEi/ARB at the time of radiation oncology consultation compared to 90 (67%) patients not taking ARBs. There were no significant differences in the distribution of key baseline variables between the two groups. The pCR rates with and without ACEi/ARB use were 36% and 43%, respectively (pZ0.39). Median OS and PFS in this group were 2.4 and 1.7 years, respectively. 3-year OS with and without ACEi/ARB use was 38.1% and 47.2% respectively, pZ0.2. Similarly, 3-year PFS was 42.9% and 47.6% respectively, pZ0.94. On multivariate analysis including use of ACEi/ARB in the model, none of the baseline characteristics impacted OS (borderline significance for N-stage, p < 0.1) and only advanced nodal status was associated with worse PFS (HRZ1.9, 95% CI 1.1-3.3, pZ0.03) with borderline significance of anatomical location and gender (p < 0.1). Conclusion: In our study, the use of ACEi/ARB was not associated with inferior pCR rates, OS or PFS. Validation in larger prospective databases with longer follow up is necessary to assess confounding effect of associated medical comorbidities on survival. If validated, then this absence of a negative impact supports their development as mitigators of radiation induced lung injury. Author Disclosure: J. Hyder: None. H. Boggs: None. M.D. Chuong: None. M. Suntharalingam: None. W. Burrows: None. N. Horiba: None. D.P. Zandberg: None. T.N. Tyer: None. E.P. Cohen: Research Grant; Department of Veterans Affairs. review of policy, planning meeting; Cancer and Kidney International Network. Z. Vujaskovic: None. P. Mohindra: None.

PURPOSE To compare efficacy in terms of pathologic response in LARC patients treated with preoperative chemoradiation, with or without a short-intense course of induction oxaliplatin. PATIENTS AND METHODS From 05/98 to 10/02, 114 patients were treated with preoperative chemoradiation (4500-5040 cGy + oral Tegafur 1200 mg/day) for cT(3)-(4)N(+/x)M(0) rectal cancer. Starting 05/01, 52 consecutive patients additionally received induction FOLFOX-4, oxaliplatin (85 mg/m(2) iv d1), 5-FU (400 mg/m(2) iv bolus d1) and 600 mg/m(2) iv continuous infusion in 22 h with leucovorin (200 mg iv) d1 and d2, every 15 days (2 cycles), followed by the previously described Tegafur chemoradiation regime. Surgery was performed in 5-6 weeks. Pathological assessment investigated post-treatment T and N status in the rectal wall and peri-rectal tissues. RESULTS Patients, tumor and treatment characteristics were comparable between groups. Incidence of pT(0) specimens was significantly increased by induction FOLFOX-4 (P = 0.006). Total T and N downstaging were 58% versus 75% and 42% versus 40%, respectively (P = ns). T downstaging of > or =2 categories was significantly superior in FOLFOX-4 group (P = 0.029). CONCLUSIONS Short-intense induction FOLFOX-4 significantly improves pathologic complete response in LARC patients treated with tegafur-sensitized preoperative chemoradiation. The 44% rate of pT(0)-(1) specimens observed in the oxaliplatin group should impulse innovative surgical approaches to promote ano-rectal sphincter conserving protocols.

To evaluate the survival rates, prognostic factors and adverse events in patients with pituitary adenomas following fractionated stereotactic-guided radiotherapy (FSRT).Fifty-six patients with pituitary adenomas were treated with FSRT; 23 patients (41.1%) had primary adenomas, 33 had recurrent disease; 24 (42.9%) with non-functional and 32 (57.1%) with functional adenomas. Using conventional fractionation, median total dose administered was 54 Gy (range: 24-56 Gy).The median follow-up was 51 months (range: 9-102) and, at the time of analysis, 49 patients were alive and disease-free, 1 patient was alive with reduced visual acuity and biochemical indications of recurrence, 2 patients had died from the disease and 1 patient had died from unrelated causes. Overall survival was 94% (50/53) and overall local tumour control was 92% (49/53). Univariate analysis indicated hormonal secretion (ACTH) and previous radiotherapy as being statistically significant. Fourteen patients (25%) had minor side-effects during treatment and 3 patients (5.4%) had late-onset events; 2 with optical neuropathy (both patients had other relevant co-existing diseases) and 1 patient had brain necrosis (re-irradiation).Fractionated stereotactic-guided radiotherapy is an effective modality for the treatment of pituitary adenomas. Care is required in patients with co-morbidities and/or previously-irradiated recurrent tumour so as to minimise late-onset secondary effects.

Intraoperative radiation therapy (IORT) has been used for over 30 years in Asia, Europe and America as a supplementary activity in the treatment of cancer patients with promising results. Modern IORT is carried out with electron beams (IOERT) produced by a linear accelerator generally used for external beam irradiation (EBRT) or a specialized mobile electron accelerator. HDR brachytherapy (HDR-IORT) has also been applied on selected locations. Retrospective analysis of clinical experiences in cancer sites such as operable pancreatic tumour, locally advanced/recurrent rectal cancer, head and neck carcinomas, sarcomas and cervical cancer are consistent with local tumour control promotion compared to similar clinical experiences without IORT. New emerging indications such as the treatment of breast cancer are presented. The IORT component of the therapeutical approach allows intensification of the total radiation dose without additional exposure of healthy tissues and improves dose-deposit homogeneity and precision. Results of the application of IORT on selected disease sites are presented with an analysis on future possibilities. To improve the methodology, clinical trials are required with multivariate analysis including patient, tumour and treatment characteristics, prospective evaluation of early and late toxicity, patterns of tumour recurrence and overall patient outcome.

Purpose Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. Patients and Methods Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. Results After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those ≥ 72 Gy (P = .003). Conclusion The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.

Intraoperative radiotherapy (IORT) is a technique where a high, single-fraction radiation dose is delivered during a surgical procedure to macroscopic tumours or tumour beds with minimal exposure of surroundings tissues which are displaced and shielded during the procedure. In this paper, the rationale for and use of IORT, both with electron beams (IOERT) and high-dose-rate brachytherapy (HDR-IORT) are discussed. For most tumours, the likelihood of obtaining local control (LC) improves when increasing doses can be administered. In many clinical situations, however, the dose that can be delivered safely to the tumour target is limited by the risk of damaging normal tissues. Special consideration is therefore given on this paper to the relationship between dose, LC and possible complications. Criteria for patient's selection and evaluation and information on sequencing and techniques are presented as well as some considerations on the need for a proper programme on quality assurance and periodical reporting of data.

The early institutional experience in the neoadjuvant treatment of potentially resectable pancreatic carcinoma using oral Tegafur as radioenhancing agent is analyzed. Fifteen patients (10 male and 5 female, mean age of 61 years) were treated over a 30-month period. Tegafur dose was 1,200 mg/d along the external radiotherapy period (45-55 consecutive days). Preoperative radiotherapy achieved a total dose of 45 to 50 Gy (1.8 Gy/d). Intraoperative electron boost (10-15 Gy) was delivered at the time of surgery. Hematologic tolerance showed a significant decrease of neutrophil and platelet counts from the outset to the end of the neoadjuvant period (p = 0.001 and p = 0.004, respectively). Five grade III vomiting episodes (33%) were also registered. In 9 patients (60%), surgical resection was performed after chemoradiation. Three complete pathologic responses (pT0 specimens) were identified; in seven cases, the resection achieved tumor-free surgical margins of the specimen. With a median follow-up of 21 months, median survival time was 17 months, with actuarial rates of 45% at 1 year and 24% at 3 years. Median survival for the resected patients was 23 months, and for the unresected patients median survival was 8 months (p = 0.02). The overall median survival in completely resected patients was 28 months, with a 71% survival rate at 1 and 3 years. It is concluded that the treatment scheme described is feasible and acceptably tolerated. The use of oral Tegafur seems to induce results similar to those of other therapeutic protocols using intravenous radioenhancing chemotherapy.

El cáncer colo-rectal es el 2º tumor en frecuencia en Europa. En el 5-10% de los casos existe infiltración de órganos urológicos. Cuando la infiltración afecta a la vejiga o a la próstata, la exenteración pelviana anterior es el tratamiento con el que se consiguen mayor porcentaje de márgenes quirúrgicos libres de tumor y mayores probabilidades de supervivencia a los 5 años. En casos muy seleccionados de infiltración prostática es posible preservar la vejiga, realizando una prostatectomía y amputación abdominoperineal en bloque cumpliendo con los requisitos quirúrgicos oncológicos y mejorando de forma importante la calidad de vida del paciente. Debido a la escasa bibliografía existente (dos artículos con 3 casos) presentamos nuestra experiencia en 2 pacientes a los que se les realizó radioquimioterapia preoperatoria citoreductora, prostatectomía y amputación abdominoperineal en bloque y radioterapia intraoperatoria. Describimos la técnica quirúrgica utilizada, que presenta diferencias sustanciales con la prostatectomía estándar y precisa de una buena coordinación entre el equipo de cirujanos y el de urólogos. Colorectal cancer in the 2nd commonest cancer in Europe. In 5-10% of cases there is infiltration of urological organs. When infiltration affects the bladder or the prostate, anterior pelvic exenteration is the treatment that achieves the largest percentage of tumor free margins and the best 5-year survival. In very select cases of prostatic infiltration, the bladder can be preserved and prostatectomy and abdominoperineal block resection are carried out fulfilling oncological surgical requirements and producing an important improvement in the patient's quality of life. Owing to the very scarse published literature (two articles with three cases) we contribute our experience of 2 patients who received cytoreducing preoperative radiochemotherapy, prostatectomy and block abdominoperineal amputation and intraoperative radiotherapy. We describe the surgical technique used, which is substantially different from standard prostatectomy and requires good coordination between surgeons and urologists.

It is difficult to conclude a clear benefit from the addition of IORT to the multimodality treatment of gastric cancer based on the studies available. Only three prospective randomized trials have been published and each varies in the approach of combining adjuvant and neoadjuvant chemotherapy and EBRT with IORT. With a complex degree of confounding factors in these and other retrospective series, it also remains difficult to identify a decrease in local recurrence rates, or an improvement in overall patient survival rates attributable to the use of IORT. Several series, however, have identified patient subsets--specifically, patients who have advanced disease with serosal extension or node-positive disease--who may be more likely to benefit from the addition of IORT to gastric resection. Finally, there is no evidence in prospective or retrospective series that there is an increased patient risk or inferior outcome caused by the addition of IORT. Limited evidence of a possible benefit in advanced disease and no evidence of a disadvantage to the use of IORT have promoted continued use and investigation in the multimodality treatment of an aggressive disease. Continued efforts in prospective randomized trials should be promoted to further delineate the efficacy of IORT and EBRT in the treatment of gastric cancer, especially in light of recently published data [30], where concurrent chemotherapy has been reported to increase survival rates in high-risk patients.

It is difficult to establish the degree of effectiveness of IORT as a component of treatment in some of the malignancies currently being treated by IORT. Locally advanced pancreatic cancer is a typical example of a neoplasm for which it has been challenging to find effective advances in treatment. The survival time of patients who have this disease is limited to 9 to 12 months (median), with a 2-year survival rate of 10% to 20% following even the most effective chemoradiation. It is perhaps overly optimistic to expect that IORT will significantly enhance survival, because currently available systemic treatment options have not meaningfully affected either overall patient survival times or the rate of distant metastasis in either the adjuvant setting or for metastatic disease. It is encouraging, however, that Willett has reported five patients with 5-year survival times in the Massachusetts General Hospital IOERT series for unresectable pancreatic cancer (C.G. Willett, personal communication, 2002). Also encouraging is the report from the Medical College of Ohio of a 5-year rate of 33% in a small group of patients with resectable pancreatic cancers treated with single IORT doses (without EBRT or chemotherapy) as the sole adjuvant to surgical resection. At the same institution, during the same time period, the same group of surgeons observed that no patient with resectable pancreatic cancer survived longer than 13 months following surgical resection alone [7]. Exciting possibilities involve the use of IORT when treating early-stage malignant disease, as is detailed in the chapter on breast cancer. The use of [table: see text] IORT as adjuvant therapy seems to be associated with an extremely low incidence of in-breast local recurrence. Whether this is because of early stage of the disease or the adjuvant EBRT is not entirely clear at the time of this writing. (The results of ongoing randomized studies may not be powered sufficiently to resolve the question.) Because the local recurrence rate currently is extremely low (only one reported recurrence), however, this finding is promising. Also exciting is the use of IORT as the sole radiation [table: see text] treatment following limited excision of breast cancer. The results of the Lanciano and Milano trials (see chapter 12) are awaited with great interest. Equally exciting is the finding of meaningful survival of 20% to 40% of patients who have local or regionally recurrent cancers when IORT is used as a component of treatment together with EBRT, maximal resection, and chemotherapy, as indicated. Many of these patients still have excessive rates of both local and distant relapse, however, necessitating the rationale for well-controlled multi-institutional studies that involve alternate systemic therapies, radiation sensitizers, among other criteria.

To analyze the patterns of failure and the toxicity profile of intraoperative electron beam radiotherapy (IOERT) after resection of soft tissue sarcomas of the extremities (STS). PATIENTS AND METHODS: Forty-five patients with extremity STS were treated with IOERT and moderate-dose postoperative radiotherapy (45-50 Gy). Twenty-six patients were treated for primary disease (PD) and 19 patients for an isolated recurrence (ILR). Tumor size was >5 cm (maximum diameter) in 36 patients (80%), and high-grade histology in PD patients was present in 14 patients (54%). In nine patients, IOERT was used alone, due to previous irradiation or patient refusal. Chemotherapy (neoadjuvant and/or adjuvant) was mainly given to high-grade tumors. RESULTS: Nine patients relapsed in the extremity (20%), and 12 patients in distant sites (28%). Actuarial local control at 5 years was 88% for patients with negative/close margins and 57% for patients presenting positive margins (P=0.04). Five patients (11%) developed neuropathy associated with the treatment. Extremity preservation was achieved in 40 patients (88%). With a median follow-up of 93 months (range: 27-143 months) for the patients at risk, 25 patients remain alive (a 7-year actuarial survival rate of 75% for PD and 47% for ILR; P=0.01). CONCLUSIONS: IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity STS. Peripheral nerves in the IOERT field are dose-limiting structures requiring a dose compromise in the IOERT component to avoid severe neurological damage.

El uso de la irradiacion parcial acelerada de la mama (IPAM) en lugar de la irradiacion total de la mama (ITM) para la terapia conservadora de la mama (TCM) es un area de intensiva investigacion clinica . El debate se ha mantenido generalmente en ambientes especializados, pero la divulgacion de esta modalidad terapeutica a la comunidad medica no especialista y al publico general requiere que esta discusion se extienda a publicaciones de amplia divulgacion entre la comunidad medica general.

EXPERIENCE WITH IORT AS INTRAOPERATIVE INTENSIFICATION THERAPY IN THE TREATMENT OF LOCALLY ADVANCED RETROPERITONEAL AND PELVIC SARCOMAS E. Velasco Sanchez1, J. L. Garcia-Sabrido1, F. Calvo2, L. Gomez Lanz1, L. Gonzalez-Bayon1, L. Rodriguez-Bachiller1, B. Diaz-Zorita1, E. Ruiz Ucar1, P. Alvarez de Sierra1 1 HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARANON, Oncological Surgery, Madrid, Spain 2 HOSPITAL GREGORIO MARANON, Oncology and Radiotherapy, Madrid, Spain

5038 Background: Androgen deprivation (AD) combined with radiotherapy (RT) is an established treatment for locally advanced prostate cancer (PCa). However, the timing and optimal duration of AD ass...

6067 Background: The approach to LAHNSCC including surgery, radiotherapy(RT), and chemotherapy (CT) lacks of significant improvements in long-term survival. In an attempt to explore tolerance and p...

To describe downstaging effects in locally advanced rectal cancer induced by 2 fluopirimidine radiosensitizing agents given through different routes in conjunction with preoperative radiotherapy.From March 1995 to December 1999, two consecutive groups of patients with cT3-4Nx rectal cancer (94% CT scan, 71% endorectal ultrasound) were treated with either (1) 45-50 Gy (1.8 Gy/day, 25 fractions) and 5-fluorouracil (5-FU) (500-1,000 mg/m2 by 24-h continuous i.v. infusion on Days 1-4 and 21-25) or (2) oral Tegafur (1,200 mg/day on Days 1-35, including weekends). Surgery was performed 4 to 6 weeks after the completion of chemoradiation.The total T downstaging rate was 46% in the 5-FU group and 53% in the Tegafur group. Subcategories were downstaged by the sensitizing agents (5-FU vs. Tegafur) as follows: pT0-1, 14% vs. 23%; pT2, 32% vs. 32%; pT3, 49% vs. 37%; pT4, 5% vs. 7%; and N(0), 74% vs. 86%. Analysis of residual malignant disease in the specimen discriminated mic/mac subgroups (mic:20% of microscopic cancer residue), with evident superior downstaging effects in the Tegafur-treated group: pTmic 23% vs. 58% (p = 0.002).When administered concurrent with pelvic irradiation, oral Tegafur induced downstaging rates in both T and N categories superior to those induced by intermediate doses of 5-FU by continuous i.v. infusion. In this pilot experience, oral Tegafur reproduced the characteristics of downstaging described previously when full doses of 5-FU have been combined with radiotherapy.

The interest of using combined MR and CT information for radiotherapy planning is well documented. However, many planning workstations do not allow to use MR images, nor import predefined contours. This paper presents a new simple approach for transferring segmentation results from MRI to a CT image that will be used for radiotherapy planning, using the same original CT format. CT and MRI images of the same anatomical area are registered using mutual information (MI) algorithm. Targets and organs at risk are segmented by the physician on the MR image, where their contours are easy to track. A locally developed software running on PC is used for this step, with several facilities for the segmentation process. The result is transferred onto the CT by slightly modifying up and down the original Hounsfield values of some points of the contour. This is enough to visualize the contour on the CT, but does not affect dose calculations. The CT is then stored using the original file format of the radiotherapy planning workstation, where the technician uses the segmented contour to design the correct beam positioning. The described method has been tested in five patients. Simulations and patient results show that the dose distribution is not affected by the small modification of pixels of the CT image, while the segmented structures can be tracked in the radiotherapy planning workstation-using adequate window/level settings. The presence of the physician is not requires at the planning workstation, and he/she can perform the segmentation process using his/her own PC. This new approach makes it possible to take advantage from the anatomical information present on the MRI and to transfer the segmentation to the CT used for planning, even when the planning workstation does not allow to import external contours. The physician can draw the limits of the target and areas at risk off-line, thus separating in time the segmentation and planning tasks and increasing the efficiency.