Biomedical subjects

Numa Cellini

Publications and source records attributed to Numa Cellini.

At least 19 recordsLinked to original sources

PubMed2007

Neoplastic mesorectal microfoci (MMF) following neoadjuvant chemoradiotherapy: clinical and prognostic implications.

BACKGROUND: Neoplastic microfoci have frequently been found in the mesorectum, with poor outcome. In this study, incidence and clinical significance of mesorectal microfoci (MMF) were analyzed in patients operated on for rectal cancer following neoadjuvant chemoradiation. METHODS: A case series of 68 patients with extraperitoneal rectal cancer treated with neoadjuvant chemoradiation and surgery (including total mesorectal excision) were investigated for presence of neoplastic MMF. RESULTS: MMF were found in 26 cases (38.2%). Increasing incidence of microfoci was statistically related to pathologic involvement of the bowel wall (P = 0.0006), Mandard's tumor regression grading (P = 0.0006), and pathologic neoplastic mesorectal involvement (P < 0.00001). None of the nine patients with complete tumor disappearance displayed both microfoci and lymph node metastasis. Only one local recurrence developed in a patient with multiple MMF. One out of nine pT0 or TRG1 patients (11.1%) had distant metastases compared with 15 out of 59 pT1-4 or TRG2-5 (25.4%, P = 0.70). CONCLUSIONS: A remarkable incidence of MMF was found following chemoradiation. However, when this therapy induced complete regression of primary tumor (pT0-TRG1), we found that node metastases and neoplastic MMF also disappeared. These features should be confirmed to assess the impact of these microfoci in treatment decision making in rectal cancers.

Adenocarcinoma↗

PubMed2006

Long-term results after neoadjuvant radiochemotherapy for locally advanced resectable extraperitoneal rectal cancer.

PURPOSE: This study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy. METHODS: Eighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision. RESULTS: Median follow-up was 108 (range, 10-169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pT and pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN. CONCLUSIONS: Long- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis.

Adult↗

PubMed2006

In vivo dosimetry by an aSi-based EPID.

A method for the in vivo determination of the isocenter dose, Diso, and mid-plane dose, Dm, using the transmitted signal St measured by 25 central pixels of an aSi-based EPID is here reported. The method has been applied to check the conformal radiotherapy of pelvic tumors and supplies accurate in vivo dosimetry avoiding many of the disadvantages associated with the use of two diode detectors (at the entrance and exit of the patient) as their periodic recalibration and their positioning. Irradiating water-equivalent phantoms of different thicknesses, a set of correlation functions F(w, l) were obtained by the ratio between St and Dm as a function of the phantom thickness, w, for a different field width, l. For the in vivo determination of Diso and Dm values, the water-equivalent thickness of the patients (along the beam central axis) was evaluated by means of the treatment planning system that uses CT scans calibrated in terms of the electron densities. The Diso and Dm values experimentally determined were compared with the stated doses D(iso,TPS) and D(m,TPS), determined by the treatment planning system for ten pelvic treatments. In particular, for each treatment four fields were checked in six fractions. In these conditions the agreement between the in vivo dosimetry and stated doses at the isocenter point were within 3%. Comparing the 480 dose values obtained in this work with those obtained for 30 patients tested with a similar method, which made use of a small ion-chamber positioned on the EPIDs to obtain the transmitted signal, a similar agreement was observed. The method here proposed is very practical and can be applied in every treatment fraction, supplying useful information about eventual patient dose variations due to the incorrect application of the quality assurance program based on the check of patient setup, machine setting, and calculations.

Humans↗

PubMed2006

Neoplastic mesorectal microfoci (MMF) following neoadjuvant chemoradiotherapy: clinical and prognostic implications.

BACKGROUND: Neoplastic microfoci have frequently been found in the mesorectum, with poor outcome. In this study, incidence and clinical significance of mesorectal microfoci (MMF) were analyzed in patients operated upon for rectal cancer following neoadjuvant chemoradiation. METHODS: A case series of 68 patients with extraperitoneal rectal cancer, treated with neoadjuvant chemoradiation and surgery (including total mesorectal excision), was investigated for the presence of neoplastic MMF. RESULTS: Mesorectal microfoci were found in 26 cases (38.2%). Increasing incidence of microfoci was statistically related to pathologic involvement of bowel wall (P = 0.0006), Mandard's tumor regression grading (P = 0.0006) and pathologic neoplastic mesorectal involvement (P < 0.00001). None of the nine patients with complete tumor disappearance displayed both microfoci and lymph node metastasis. Only one local recurrence developed in a patient with multiple MMF. Out of 9 pT0 or TRG1 patients, 1 (11.1%) had distant metastases, compared to 15 out of 59 pT1-4 or TRG2-5 (25.4%, P = 0.70). CONCLUSIONS: A remarkable incidence of MMF was found following chemoradiation. However, when this therapy induces complete regression of primary tumor (pT0-TRG1), node metastases and neoplastic MMF could also disappear, as shown in our cases. These features should be confirmed because they could significantly impact the treatment decision-making of rectal cancers.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results.

PURPOSE: To evaluate long-term effects of chemoradiation and intraluminal brachytherapy in terms of local control, disease-free survival, overall survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: Twenty-two patients with unresectable (17 patients) or residual (5 patients) nonmetastatic extrahepatic bile tumors received external beam radiation therapy (39.6-50.4 Gy) between 1991 and 1997. In 21 patients, 5-fluorouracil (96-h continuous infusion, Days 1-4, 1,000 mg/m2/day) was administered. Twelve patients received a boost of intraluminal brachytherapy with 192Ir wires (30-50 Gy) 1 cm from the source axis. RESULTS: During external beam radiotherapy, 10 patients (45.4%) developed Grade 1 to 2 gastrointestinal toxicity. In patients with unresectable tumor who could be evaluated, the clinical response was 28.6% (4 of 14). Two patients showed complete response. In all 22 patients, median durations of local control, disease-free survival, and overall survival were 44.5 months, 16.3 months, and 23.0 months, respectively. Two patients who received external beam radiation therapy and intraluminal brachytherapy developed late duodenal ulceration. In patients with unresectable tumors, median survival was 13.0 months and 22.0 months in those treated with and without brachytherapy, with 16.7% and no 5-year survival, respectively (p=0.607). Overall 5-year survival was 18.0%: 40% and 11.7% in patients treated with partial resection and in those with unresectable tumor, respectively (p=0.135). CONCLUSION: This study confirmed the role of concurrent chemoradiation in advanced biliary carcinoma; the role of intraluminal brachytherapy boost remains to be further analyzed in larger clinical trials.

Adult↗

PubMed2005

The prognostic effect of clinical staging in pancreatic adenocarcinoma.

BACKGROUND: The importance of pancreatic cancer staging is uncertain. The aim of this report was to evaluate the accuracy of combined standard imaging techniques in predicting the pathologic stage and to evaluate the prognostic effect of clinical staging to identify patient groups in which laparoscopy and laparotomy could be beneficial. METHODS: Fifty-four patients were included in this analysis. The techniques used for clinical staging were endoscopic retrograde cholangiopancreatography, abdominal computed tomographic scan, and ultrasonography. All patients underwent both clinical and surgical/pathologic staging. A comparison was performed between presurgical stage and surgical/pathologic stage. The prognostic effect of different factors on survival was evaluated with both univariate (log-rank) and multivariate (Cox) analysis. RESULTS: Sensitivity and specificity for vascular involvement were 73.9% and 96.3%, respectively. Sensitivity and specificity for nodal involvement were 63.6% and 95.4%, respectively. A total of 33.3% of patients showed a higher than expected pathologic stage, and 3.7% showed a lower than expected pathologic stage, by comparing clinical and pathologic evaluation. A highly significant correlation was observed between clinical T stage (P = .0067) and tumor diameter (P = .0037) and patient survival. Maximal prognostic differentiation was observed by dividing patients into two groups based on imaging results: group A (favorable prognosis) and group B (unfavorable prognosis). The median survival was 25.1 and 8.0 months for group A and B, respectively. Five-year survival was 20.1% and 0%, respectively (multivariate analysis: P = .0007). CONCLUSIONS: Integrated standard imaging studies achieved reasonable diagnostic accuracy in our analysis. A single classification based on clinical stage and tumor diameter evaluated by imaging predicts prognosis in patients with pancreatic carcinoma.

Adenocarcinoma↗

PubMed2005

The multidisciplinary rectal cancer treatment: main convergences, controversial aspects and investigational areas which support the need for an European Consensus.

BACKGROUND AND PURPOSE: During the past decades staging and treatment of rectal cancer are used different in Europe and in North America. To promote a process to integrate the daily practice with the best evidence of the literature an International Conference was organized in Italy. Agreement between Experts, Centres, and specialists who participated in the Conference are reported. METHODS: Five aspects were analyzed and a questionnaire was tailored for this purpose. The questionnaire had 159 questions. During the Conference, at the beginning of each Session, the moderators showed the answers from the Experts and the Centres, and, at the end of the session, the audience voted in all controversial issues. Agreements were scored at three levels: minimum, if it was between 51 and 74% of votes for each group; moderate, between 75 and 94%; large, more than 94%. RESULTS: The main results are: staging: endoanal ultrasound was considered as mandatory in T staging, in the evaluation of sphincter infiltration, and in the restaging of T after chemoradiotherapy (chRT). Magnetic Resonance Imaging is mandatory in the evaluation of mesorectal fascia infiltration. Endoscopy had a moderate agreement for the definition of tumour location, and the barium enema as optional. Digital rectal examination is complementary for staging and PET-CT investigational for T, N and yT staging. Preoperative radiotherapy: for T4 stage chRT was always the preferred treatment, often with moderate agreement, for any tumour location and N status. For T3, chRT received the same agreement except for high location and N0-N1. For T2 stage, N2 and positive nodes outside the mesorectum, chRT received minimum agreement for low and middle tumours; for high tumours only positive nodes outside the mesorectum was agreed upon. Preoperative radiotherapy, negative specimen and sphincter preservation: chRT was agreed by many for all T stages and N presentations of lower third tumours, except for T1-2 N0-N1. Postoperative treatments: the selection for these treatments often received moderate agreement according to the infiltration of surrounding organs, positive nodal status and circumferential radial margins. Therapy of metastatic disease: an agreement was found for FOLFOX as first-line therapy and for FOLFIRI as second-line, although comparative studies show similar activity of FOLFOX and FOLFIRI regimens. CONCLUSIONS: This process represents an expertise opinion process that may contribute to increased scientific debate and to promote the development of 'guidelines', 'clinical recommendations' and ultimately a Consensus on the evolving approach to rectal cancer treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Chemoradiation with raltitrexed and oxaliplatin in preoperative treatment of stage II-III resectable rectal cancer: Phase I and II studies.

PURPOSE: Two separate studies were conducted, the first to evaluate the maximal tolerated dose and the second the efficacy of raltitrexed plus oxaliplatin in conjunction with preoperative chemoradiation in patients with resectable T3 rectal carcinoma. METHODS AND MATERIALS: A total of 48 patients received radiotherapy (50 Gy) administered to the posterior pelvis 5 d/wk for 5 weeks. Combination raltitrexed (3 mg/m(2)) and oxaliplatin (60 to 130 mg/m(2)) was administered on Days 1, 19, and 38. RESULTS: The recommended dose of oxaliplatin is 130 mg/m(2) (maximal tolerated dose not reached). No patients developed Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 9 patients (18.7%). It was hematologic in 1 patient and GI in 1 patient; 7 patients had an asymptomatic increase of transaminase. Surgery was performed in 47 (98%) of 48 patients. Of the 47 patients, 42 underwent sphincter-saving surgery; in 19, the tumor at diagnosis was located <30 mm from the anorectal ring. Chemoradiation in combination with raltitrexed and oxaliplatin produced high rates of tumor response. The overall tumor downstaging rate was 73% for T and N stages. A complete pathologic tumor response (pT0) or microscopic tumor foci (pTmic) was observed in 28 patients. The tumor regression grade (TRG), using the Mandard scoring system, was TRG1 in 16 patients (43.2%), TRG2 in 12 (32.4%), TRG3 in 12 (32.4%), TRG4 in 6 (16.2%), and TRG5 in 1 patient (2.7%). CONCLUSION: Raltitrexed plus oxaliplatin combined with pelvic radiotherapy was effective and well tolerated in patients with resectable T3 rectal carcinoma.

Aged↗

PubMed2004

Chemoradiation with raltitrexed (Tomudex) in preoperative treatment of stage II-III resectable rectal cancer: a phase II study.

PURPOSE: To evaluate the impact of preoperative chemoradiation with raltitrexed (Tomudex(1)) on tumor response, sphincter preservation, and toxicity in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Between 1998 and 2002, 54 consecutive patients with Stage T3 or T2N+ resectable rectal carcinoma were treated with preoperative chemoradiation, i.v. bolus of raltitrexed on Days 1, 19, and 38 and concurrent 50 Gy external beam radiotherapy. Surgery was performed 6-8 weeks after the end of chemoradiation. RESULTS: No patients had Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 16.6% of cases and was hematologic in 6 patients and GI in 2. The overall clinical response rate was 88.8%, with a complete response in 5.5%, partial response in 83.3%, and no change in 9.2%. No patient showed disease progression. All patients underwent surgery. Sphincter saving was obtained in 83.3% of patients. No perioperative mortality occurred, and the perioperative morbidity rate was 5.5%. Of 20 resected patients (37%) who were candidates for abdominoperineal resection at diagnosis (anorectal ring distance < or =30 mm), 13 (65%) underwent a sphincter-saving procedure. At pathologic examination, 13 (24%) of 54 patients had a complete pathologic response (pT0) and 10 (18.5%) had rare isolated residual cancer cells (pT, microscopic foci). Overall, 42.5% had major downstaging. The tumor regression grade (TRG), using Mandard's score system, was also applied and was TRG1 in 13 patients, TRG2 in 11, TRG3 in 20, and TRG4 in 10 patients; no patient had TRG5. CONCLUSION: The use of raltitrexed in a neoadjuvant chemoradiation schedule promoted high pathologic tumor downstaging and use of a sphincter-saving procedure. The low toxicity profile supports the rationale to explore raltitrexed combined with other drugs with different biologic targets.

Aged↗

PubMed2004

5-fluorouracil-based chemoradiation in unresectable pancreatic carcinoma: Phase I-II dose-escalation study.

PURPOSE: A Phase I-II dose-escalation study was performed to evaluate the possible impact of the dose on response, toxicity, pain relief, and outcome in patients with unresectable pancreatic carcinoma. METHODS AND MATERIALS: A total of 50 patients entered the study. The external beam radiotherapy (RT) dose was 39.6 Gy in the first 15 patients, 50.4 Gy in the next 15 patients, and 59.4 Gy in the remaining 20 patients, at five 1.8-Gy fractions weekly. During external beam RT, patients received concurrent continuous infusion of 5-fluorouracil (1000 mg/m(2) on Days 1-4 and 21-24). Patients were evaluated for toxic reactions, local disease control, survival, and pain relief. RESULTS: No treatment-related deaths occurred from acute toxicity. Four patients required a temporary treatment interruption because of acute hematologic (2 patients) or GI (2 patients) toxicity, not correlated with the delivered RT dose. Three patients (6%) developed late toxicity (duodenal ulcer in 2 and duodenal stenosis in 1). All patients who developed late toxicity had received a dose of 59.4 Gy. At univariate analysis, only the RT dose correlated significantly with the incidence of late toxicity (at 2 years, 39.6-50.4 Gy resulted in 0% and 59.4 Gy resulted in 58.2%; p = 0.023). At multivariate analysis, the RT dose also showed a trend with the incidence of late side effects (p = 0.052). Overall, 6 patients had a partial response (12%) and 44 (88%) had no change. The overall response rate was 8.0% (95% confidence interval, 1.5-20.5%). The rate of response was not different in the three groups. In-field locoregional disease progression was seen in 7 patients (14.0%). Distant relapse was documented in 34 patients (68.0%). None of analyzed variables, in particular, the RT dose delivered, showed a statistically significant correlation with objective response, local control, incidence of metastasis, disease-free survival, or overall incidence of pain symptoms after therapy. The whole group median survival was 9 months. The actuarial survival rate at 1, 2, and 3 years was 31.3%, 2.8%, and 0.0%, respectively. None of analyzed parameters correlated significantly with survival at univariate or multivariate analysis. CONCLUSION: In a Phase I-II study, the association of high RT doses with the incidence of severe toxicity in the treatment of unresectable pancreatic carcinoma was confirmed. Furthermore, this dose-escalation study did not document a clearcut correlation, using 5-fluorouracil-based chemoradiation, between the radiation dose and clinical outcome.

Analysis of Variance↗

PubMed2004

An application of visible human database in radiotherapy: tutorial for image guided external radiotherapy (TIGER).

BACKGROUND AND PURPOSE: Three-dimensional conformal radiotherapy and intensity modulated radiotherapy allow accurate dose delivery on target volumes. Due to the different background among specialists involved in target volume definition, the contouring emerges as one of the most questionable steps in treatment planning procedures. A software tool devoted to contouring training, named tutorial for image guided external radiotherapy ('TIGER'), based on the Visible Human Project images data-set, is described. MATERIALS AND METHODS: TIGER is addressed to facilitate the learning of axial anatomical images, to promote the training and reproducibility in contouring process, to allow the availability of a tool to enhance the 'drill and practice' approach in training programs. TIGER includes three different environments: Anatomic tutorial devoted to facilitate a self-learning approach to axial body sections; Contouring tutorial addressed to practice contouring process of anatomical structures and to undergo a test program prepared by tutors; Teacher's tools to offer to tutors the opportunity to insert new outlines in TIGER-database, according to local needs or conventions, and to use them in tutorial programs. TIGER-database is grouped in six main anatomical sections: head and neck, male thorax, female thorax, abdomen, male pelvis, and female pelvis. Overall 432 corresponding CT-VH images and 1189 contours of 134 different anatomical structures and lymphatic drainage areas are available. The access to the TIGER software is allowed by ESTRO web site (http://www.estro.be). CONCLUSIONS: TIGER provides an interactive human anatomy cross-sectional oriented source to facilitate the interpretation of CT scan images usually contoured in daily practice. It offers a drill tool to facilitate the learning of a reproducible contouring procedure.

Databases as Topic↗

PubMed2004

Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between neoadjuvant and adjuvant hormonotherapy.

INTRODUCTION: The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy. PATIENTS AND METHODS: One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present. RESULTS: Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded. CONCLUSIONS: In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control.

Antineoplastic Agents, Hormonal↗

PubMed2004

Concomitant radiochemotherapy plus surgery in locally advanced cervical cancer: update of clinical outcome and cyclooxygenase-2 as predictor of treatment susceptibility.

OBJECTIVE: We have updated our findings on the efficacy of concomitant radiochemotherapy plus radical surgery in a larger series of patients (n = 54) with locally advanced cervical cancer (LACC). We also investigated the role of cyclooxygenase-2 (COX-2) in this clinical setting. METHODS: Radiotherapy was administered to the whole pelvic region (1.8 Gy/day, totaling 39.6 Gy) in combination with cisplatin (20 mg/m2) and 5-fluorouracil (1,000 mg/m2) (both on days 1-4 and 27-30). Radical surgery was performed 5-6 weeks after the end of treatment. RESULTS: A clinical complete or partial response was observed in all 53 evaluable patients (75.5 and 24.5%, respectively). At pathological examination, 23 of 51 patients (45.1%) undergoing radical surgery showed complete response to treatment, 18 patients (35.3%) only had microscopic residual disease, 6 patients (11.7%) had a partial response and 4 (7.8%) had no change in their disease. When logistic regression was applied, the FIGO stage (chi2 = 5.28, p = 0.021) and tumor to stroma COX-2 ratio (chi2 = 4.72, p = 0.029) retained an independent role in the prediction of the pathologic response to treatment. The 3-year disease-free survival (DFS) was 75.2%, with local relapse-free survival of 86.2% and metastasis-free interval of 89.9% at 3 years. Cases with a high COX-2 ratio showed a shorter DFS than cases with a low COX-2 ratio (p = 0.016). A direct association was shown between COX-2 ratio values and risk of recurrence, as assessed by Cox analysis using COX-2 ratio values as a continuous covariate (chi2 = 3.94, p = 0.047). CONCLUSION: This study confirms the possibility of achieving a very high rate of pathological responses in LACC patients administered chemoradiation plus surgery (3-year DFS 75.2%). Moreover, COX-2 status may play a role in the prognostic characterization and prediction of tumor response.

Adult↗

PubMed2003

Chemoradiation of unresectable pancreatic carcinoma: impact of pretreatment hemoglobin level on patterns of failure.

AIM: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. PATIENTS AND METHODS: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m(2)/day, continuous i.v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs nC1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis (> or = 5 kg vs < 5 kg), epigastric-lumbar pain at diagnosis (yes vs no), maximum tumor diameter (< 40 mm vs > or = 40 mm). RESULTS: Pretreatment Hb ranged between 9.6 and 15.0 g/dl. No statistically significant differences were observed as for clinical response and local control between patients with an Hb < or = 11.5 g/dl and those with an Hb > 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb < or = 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0,010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb < or = 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb < or = 11.5 and > 11.5 g/dl; respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). CONCLUSION: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed between pretreatment Hb levels and metastasis-free survival, disease-free survival, and overall survival.

Adult↗

PubMed2003

Combined-modality therapy in locally advanced primary rectal cancer.

PURPOSE: Patients with unresectable, locally advanced rectal cancer are reported to have a dismal prognosis. The aim of this study was to analyze the effect of combined-modality therapy on clinical outcome. METHODS: From March 1990 to December 1997, 43 patients (28 males; median age, 62 years; median follow-up, 74 months) with locally advanced (T4 and/or N3) nonmetastatic rectal cancer received external-beam radiation (23.6 plus 23.6 Gy (split course), 8 patients; 45 Gy, 35 patients) plus 5-fluorouracil (96-hour continuous infusion, Days 1-4, at 1,000 mg/m(2)/day) and mitomycin C (10 mg/m, intravenous bolus, Day 1). Concomitant chemotherapy was repeated at the beginning of the second course (split-course group) or in the last week of radiotherapy (continuous-course group). After 6 to 8 weeks, patients were evaluated for surgical resection and intraoperative radiation therapy (10 to 15 Gy). Thereafter, adjuvant chemotherapy (5-fluorouracil plus leucovorin, 6-9 courses) was prescribed. RESULTS: During chemoradiation, 5 patients (11.6 percent) developed Grade 3 to 4 hematologic toxicity. After chemoradiation, 29 patients (67.4 percent) had an objective clinical response (complete response, 2.3 percent; partial response, 65.1 percent). Thirty-eight patients underwent radical surgery (anterior resection, 24 patients; abdominoperineal resection, 14 patients; intraoperative radiation therapy boost on the tumor bed, 19 patients), and 2 patients had partial tumor resection. No perioperative deaths occurred in the patient group. Five-year survival and local control rates were 59.9 and 69.1 percent, respectively. Distant metastasis occurred in 44.2 percent of patients. Statistically significant relationships between intraoperative radiation therapy and local control (P = 0.0104), radical surgery and survival (P = 0.0120), and adjuvant chemotherapy and disease-free survival (P = 0.0112) were observed. CONCLUSIONS: Our data suggest that combined-modality therapy was relatively well tolerated and resulted in good local control and survival. With regard to the impact of surgical resection on survival, additional studies aimed at improving the local response rate are necessary, whereas the positive impact of intraoperative radiotherapy on local control appears to justify the inclusion of this therapeutic modality in prospective multi-institutional trials.

Adult↗

PubMed2003

Pain relief with short-term irradiation in locally advanced carcinoma of the pancreas.

OBJECTIVES: To evaluate whether a short radiation treatment (30 Gy, 3.0 Gy/fraction) had analgesic efficacy in patients with unresectable pancreatic carcinoma. METHODS: Twelve patients were included in this analysis. Before starting and at four weeks after radiation therapy, pain intensity was evaluated and analgesic drug therapy was adjusted until a 0-3 pain score was reached (WHO). RESULTS: No radiotherapy interruptions, no hospitalisation due to toxic reactions, and no severe toxicity were observed. Six patients (50%) had pain control without pharmacological therapy, three patients (25%) reduced their use (35%-72%) of analgesics, while in the remaining three patients (25%) there was no change in analgesic use. Overall, mean reduction in the use of analgesics was 63.1% +/- 43.8%. During follow-up (44 months), two patients (16.7%) showed a worsening of pain that required increased analgesia; in one patient, percutaneous splanchnicectomy was necessary. CONCLUSION: In patients excluded from standard concomitant chemoradiation, hypofractionated-accelerated radiotherapy is feasible and results in pain relief in most patients, documented as a reduced need for analgesics.

Actuarial Analysis↗

PubMed2002

Analysis of intraprostatic failures in patients treated with hormonal therapy and radiotherapy: implications for conformal therapy planning.

PURPOSE: Conformal therapy of prostate cancer is based on high-dose irradiation to the entire prostate gland. The aim of this study was to analyze the pattern of intraprostatic recurrence in patients undergoing external beam radiotherapy (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses are adequate to control microscopic disease outside the primary tumor and therefore whether high-dose irradiation can be exclusively focused on the macroscopic disease. METHODS AND MATERIALS: The clinical and radiologic reports of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with hormonal therapy were evaluated. In all patients, before and after therapy, the size and site of the primary neoplasm within the prostate were assessed by clinical examination and imaging studies. RESULTS: With a median follow-up of 45 months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve patients had an intraprostatic recurrence, with the appearance of a new nodule (in 5 patients with a complete response after therapy) or increased nodular size compared with the minimal size (in the 7 other patients). In all patients, on the basis of a semiquantitative evaluation of the site of recurrence, this was shown to originate within the initial tumor volume. CONCLUSION: The results of this analysis seem to confirm some histologic findings observed in patients undergoing prostatectomy for local recurrence after radiotherapy that suggest that local recurrence usually originates in the primary tumor rather than in focal prostatic intraepithelial neoplasia. This observation might justify the application of conformal therapy procedures aimed at identifying the gross tumor volume, in the phase of boost, exclusively with the primary tumor.

Aged↗

PubMed2002

Phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with inoperable non-small-cell lung cancer.

PURPOSE: To report the evidence of a phase I trial planned to determine the maximum-tolerated dose (MTD) and related toxicity of weekly gemcitabine (GEM) and concurrent radiotherapy in patients with non--small-cell lung cancer (NSCLC). In addition, the response to treatment was evaluated and reported. PATIENTS AND METHODS: Thirty-six patients with histologically confirmed NSCLC deemed unresectable because of advanced stage were observed and treated according to a combined chemoradiation protocol with GEM as chemotherapeutic agent. GEM was given weekly for 5 consecutive weeks as a 30-minute intravenous infusion concurrent with radiotherapy (1.8 Gy/d; total dose, 50.4 Gy). The initial dose was 100 mg/m(2). Pulmonary, esophageal, cardiac, hematologic, and skin toxicities were assessed. The dose of GEM was increased by 50 mg/m(2) up to a dose of 250 mg/m(2); an additional increase by 25 mg/m(2) up to the MTD was planned and realized. Three patients were enrolled for each dose level. RESULTS: Dose-limiting toxicity was identified for the 375-mg/m(2) level with two episodes of grade 2 esophagitis and two of grade 3 pulmonary actinic interstitial disease. The weekly dose of GEM 350 mg/m(2) was well tolerated. CONCLUSION: A weekly GEM dose of 350 mg/m(2) concurrent with radiotherapy was well tolerated. Promising results regarding response to treatment were observed and reported.

Adult↗