Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for patients with locally advanced pancreatic carcinoma, and can be combined with radiochemotherapy and intra-arterial plus systemic chemotherapy. METHODS: This observational study compared two groups of patients with locally advanced pancreatic carcinoma treated with either primary RFA (group 1) or RFA following any other primary treatment (group 2). RESULTS: Between February 2007 and May 2010, 107 consecutive patients were treated with RFA. There were 47 patients in group 1 and 60 in group 2. Median overall survival was 25·6 months. Median overall survival was significantly shorter in group 1 than in group 2 (14·7 versus 25·6 months; P = 0·004) Patients treated with RFA, radiochemotherapy and intra-arterial plus systemic chemotherapy (triple-approach strategy) had a median overall survival of 34·0 months. CONCLUSION: RFA after alternative primary treatment was associated with prolonged survival. This was further extended by use of a triple-approach strategy in selected patients. Further evaluation of this approach seems warranted.

Fiber intake and pancreatic cancer risk: a case-control study.

BACKGROUND: Scanty and inconsistent studies are available on the relation between dietary fiber intake and pancreatic cancer. A case-control study was carried out in northern Italy to further investigate the role of various types of dietary fibers in the etiology of pancreatic cancer. PATIENTS AND METHODS: Cases were 326 patients with incident pancreatic cancer, excluding neuroendocrine tumors, admitted to major teaching and general hospitals during 1991-2008. Controls were 652 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for intake quintiles of different types of fiber after allowance for total energy intake and other potential confounding factors. RESULTS: Total fiber intake was inversely related to risk of pancreatic cancer (OR=0.4 for highest versus lowest quintile of intake; 95% CI 0.2-0.7). An inverse association emerged between pancreatic cancer and both soluble (OR=0.4; 95% CI 0.2-0.7) and total insoluble fiber (OR=0.5; 95% CI 0.3-0.8), particularly cellulose (OR=0.4; 95% CI 0.3-0.7) and lignin (OR=0.5; 95% CI 0.3-0.9). Fruit fiber intake was inversely associated with pancreatic cancer (OR=0.5; 95% CI 0.3-0.8), whereas grain fiber was not (OR=1.2; 95% CI 0.7-2.0). CONCLUSIONS: This study suggests that selected types of fiber and total fiber are inversely related to pancreatic cancer.

Multimodality approach in extra cervical locally advanced cervical cancer: chemoradiation, surgery and intra-operative radiation therapy. A phase II trial.

BACKGROUND: The goal of this study was to determine the rational of radical surgery with intra-operative high-dose radiotherapy after chemoradiation (RT-CT) in extra cervical locally advanced cervical cancer (LACC) patients. METHODS: Between 2000 and 2007, 42 LACC (stage IIA bulky-IVA) patients were treated at the Gynecologic Oncology Unit of the C.R.O. of Aviano in a Phase II Clinical Trial. Radiotherapy was administered to the whole pelvic region (50.4 Gy in 28 fractions) in combination with cisplatin (60 mg/mq) plus 5FU (750 mg/mq for 4 days) on first and fifth week of RT. Radical surgery with Intra-Operative Radiation Therapy (IORT) was performed 6-8 weeks after the end of RT-CT treatment. RESULTS: After RT-CT, 35/42 patients (83%) underwent radical surgery and IORT treatment. At pathologic examination 8/35 (23%) patients showed complete response, while the rest (27/35) had residual disease either microscopic (17/27) or gross (10/27). The 5-year disease free survival (DFS) and the 5-year overall survival (OS) were 46% and 49% respectively. There were significant better DFS and OS when residual tumor was absent or limited to the cervix, respectively 78% versus 16% and 81% versus 20% (p < 0.001). All recurrences occurred within 24 months from treatment. CONCLUSIONS: RT-CT followed by surgery and IORT in LACC patients seems to be active in a subgroup of patients with pathological complete response to treatment or partial response with residual tumor limited to the cervix.

Tobacco smoking, alcohol consumption and pancreatic cancer risk: a case-control study in Italy.

In Italy, pancreatic cancer accounts for approximately 5% of cancer-related deaths. Tobacco smoking is the major established risk factor for this cancer, whereas the role of alcohol consumption is open to debate. Between 1991 and 2008, we conducted a hospital-based case-control study on pancreatic cancer in northern Italy. Cases were 326 patients (median age 63 years) with incident pancreatic cancer admitted to major general hospitals. Controls were 652 patients (median age 63 years) with acute non-neoplastic conditions admitted to the same hospital network of cases. Multiple logistic regression was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI). Pancreatic cancer was associated to current smoking (OR=1.68; 95% CI: 1.13-2.48), and the risk rose with increasing number of cigarettes/day (OR=2.04; 95% CI: 1.14-3.66 for > or = 20 cigarettes/day). No association emerged for former smokers (OR=0.98; 95% CI: 0.66-1.45). Alcohol consumption was associated to increased pancreatic cancer risk, but ORs were significant only among heavy drinkers (ORs: 2.03 and 3.42 for 21-34 and > or = 35 drinks/week, respectively). Pancreatic cancer risk was 4.3-fold higher in heavy smokers (> or = 20 cigarettes/day) and heavy drinkers (> or = 21 drinks/week) in comparison with never smokers who drunk < 7 drinks/week, which is compatible with an additive effect of these exposures. In conclusion, we found that tobacco smoking and alcohol drinking are two independent risk factors for pancreatic cancer which may be responsible for approximately one third of these cancers in our population.

A case of Lemierre's syndrome following Epstein-Barr virus infection.

Lemierre's syndrome, or necrobacillosis, is a life-threatening septic thrombophlebitis of the internal jugular vein. The causative organism is Fusobacterium necrophorum. Here we report a case of Lemierre's syndrome in a young male and describe the clinical presentations and treatment. Epstein-Barr virus (EBV) was a suspected predisposing factor in this case.

Ifosfamide in the adjuvant therapy of soft tissue sarcomas.

Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).

Intraoperative radiation therapy for retroperitoneal soft tissue sarcomas.

Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.

Prognostic factors in soft tissue sarcomas: a study of 395 patients.

AIMS: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas. METHODS: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997. RESULTS: Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival. CONCLUSIONS: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival.

Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma.

PURPOSE: The current standard local treatment for nonresectable pancreatic carcinoma is radiotherapy (RT) with concurrent 5-fluorouracil (5-FU); however, the optimal schedule for 5-FU administration has not been fully established. In this study, we report on our experience with the combination of RT and continuous infusion 5-FU in a group of patients with locally nonresectable pancreatic carcinoma. METHODS AND MATERIALS: Forty-two patients with adenocarcinoma of the pancreas were enrolled in a prospective clinical trial. RT was delivered using a four-field technique to a total dose of 59.4 Gy in 33 fractions. 5-FU was given through a central venous catheter at a dose of 300 mg/m(2)/day, 7 d/wk, throughout the entire course of RT. RESULTS: All patients completed the RT as planned, and 33 (78%) completed the full regimen of chemotherapy. Ten patients (23%) had a partial response, and 32 (77%) had stable disease. Subjective response, defined as the disappearance of symptoms observed at diagnosis, was also evaluated. Two patients (6%) had a complete, and 24 (75%) a partial, remission of symptoms. The median time to progression was 6.2 months, and the median survival time was 9.1 months. CONCLUSIONS: In terms of local control, the results of our study, with RT and protracted 5-FU infusion, compare well with those of other studies using RT and bolus 5-FU. The control of distant metastatic disease remains an open issue. However, the palliation of symptoms achieved by our treatment schedule in patients with a very poor prognosis and severe symptoms may be regarded as a positive result.

Risk factors for endometrial cancer according to familial susceptibility.

Endometrial cancer (EC) shares some environmental or genetic risk factors with colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis colorectal cancer) and, in this syndrome, it has the same inheritance pattern as CRC. Neoplastic family history and clinical features were evaluated in women with EC in a health care district (Pordenone Province) in Northeastern Italy from 1990 to 1995, to examine the proportion of patients with hereditary cancer and the relation with clinical characteristics of EC. We interviewed 215 patients with EC (average age 61 years, range 35-88) in relation with some risk factors (age, weight, diabetes, menstrual and reproductive pattern, synchronous and metachronous neoplasms) and we obtained their family pedigree. Twenty-nine patients (13.5%) had a CRC family history, 66 (30.7%) showed an aspecific cancer aggregation in their families and more than half (120, 55.8%) had a negative cancer family history. Family pedigrees were consistent with a dominant inherited cancer pattern in 8 patients (3.7%) belonging to the CRC-related family history group. A different pattern of family history distribution emerged in relation with age (< 55 vs. > or = 55, p < 0.001) and body mass index (BMI) (< 26 vs. > or = 26, p = 0.002). Patients with a CRC pedigree were more numerous in the younger group, in the group with lower BMI and in pre-menopausal women.

Postoperative radiotherapy and surgery in stage I endometrial carcinoma: a 10-year experience.

BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery plus adjuvant Irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic node dissection was performed. RESULTS: The overall 5-year survival was 88%. Three patients had local failure. Ten patients with local control of disease had distant metastases and 2 had local and distant recurrences. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well tolerated treatment which can achieve good local control in high-risk stage I endometrial carcinoma. The control of distant metastases remains an open issue.

Solitary thyroid metastasis from a renal cell carcinoma diagnosed and treated 12 years before: a case report.

The authors report a case of a solitary thyroid metastasis in a 62-year-old woman. The clinical history of the patient and the histologic findings are consistent with a renal origin of the tumor.

Endometrial stage I carcinoma treated with surgery and adjuvant irradiation: a retrospective analysis.

AIMS AND BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery and adjuvant irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy in 40 patients. Pelvic and para-aortic node dissection was performed in 19 patients and lymph node sampling in 5. RESULTS: Overall 5-year survival was 85%. One patient had local failure, and 5 patients with local control of disease had distant metastases. Toxicity was mild and transient. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well-tolerated treatment that can achieve a good local control in high risk, stage I, endometrial carcinoma. The control of distant metastases remains an open question.

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers. A single-institution study.

BACKGROUND: Patients with advanced, inoperable head and neck cancers have cure rates of approximately 10-15%. In these patients, concomitant chemoradiotherapy seems to improve local control and survival. 5-Fluorouracil (5-FU) administered by continuous infusion and cisplatin plus concomitant conventional radiation therapy may be promising in treating advanced, inoperable head and neck cancers. METHODS: Forty-five evaluable patients with primary nonmetastatic, inoperable head and neck cancers were treated. From January 1987 to April 1988, the patients were treated with cisplatin plus radiation therapy (Group 1) and from May 1988 to November 1990, they were treated with the same combination plus 5-FU, given in continuous infusion (Group 2). Clinical and pathologic responses were assessed after radiation therapy was completed. Patients who relapsed underwent salvage surgery, if possible. The disease free and overall survival rates of the patients were evaluated. RESULTS: The overall response rate (complete and partial response) was 93%, 60% of which comprised complete remissions. Despite the high response rates obtained in the two groups, the time to progression for complete responses and the median survival time were unsatisfactory (13 [Group 1] and 10 months [Group 2] and 17 [Group 1] and 16 months [Group 2], respectively). The toxicity rate from the two treatments was not relevant. A Grade II mucositis, according to the World Health Organization, was found in 25 patients, and the treatment was interrupted for 7-10 days in 5. CONCLUSIONS: In this study, despite an improvement in the number of complete responses, the chemotherapeutic regimen with or without 5-FU did not prolong the overall patient survival significantly.

[Combined surgical and radiotherapy treatment in endometrial cancer]. / Il trattamento combinato chirurgico e radioterapico del cancro dell'endometrio.

Early stage endometrial carcinoma is usually treated by surgery and radiotherapy if there is a substantial risk of recurrence. The aim of this study was to evaluate early and late toxicity, to determine the sites of recurrence and the prognostic factors which were statistically correlated with survival in patients who were treated with surgery plus external beam radiotherapy. MATERIALS AND METHODS. We have carried out a retrospective analysis of the records of 87 patients treated with hysterectomy plus external beam pelvic radiotherapy (50 Gy/28 Fractions), at the Radiotherapy Division of the CRO Aviano PN Italy, between 1985 and 1990. The median length of follow-up was 32.42 months. RESULTS. The treatment was well tolerated. The median time to recurrence was 6.56 months. There were 4.7% local, 5.8% distant and 3.5% local plus distant recurrences. As of May 1993 83.2% of the patients were still alive. All deaths occurred within two years from the beginning of treatment. The prognostic factors which were significantly correlated with survival were the stage of the disease (p = 0.0479), depth of myometrial invasion (p = 0.0429), age greater than 64 years (p = 0.0357) and performance status < = 80 at diagnosis (p = 0.0002). CONCLUSIONS. Our study confirms that post operative external beam pelvic RT is well tolerated and effective in achieving a good locoregional control. All the factors investigated were prognostic for survival, except histological grade, lymph node involvement and RT dose.

Results of three consecutive combined treatments for malignant gliomas. Ten-year experience at a single institution.

Between 1978 and 1988, 108 consecutive patients with malignant gliomas were treated. The patients were divided into 3 groups as follows: Group I, surgery if possible, otherwise biopsy followed by whole-brain irradiation to a total dose of 34 Gy in 4 fractions, VCR (2 mg i.v.), and BCNU (80 mg/m2 i.v.) repeated every 6 weeks; Group II received irradiation as Group I plus VP16 (75 mg/m2) every 3 weeks and BCNU (50 mg/m2 i.v.) every 6 weeks; Group III received 60 Gy in 30 fractions to the tumor bed plus VCR (2 mg i.v.), BCNU (50 mg/m2 i.v.), and CDDP (15 mg/m2 i.v.) every 6 weeks. In group I, 28 patients had stable disease (SD) and 2 patients showed disease progression (PRO). Median survival time was 9 months (range 1-18). In Group II 22 SD's were observed. Median survival time was 6 months (2-16). In the third group of patients 29 SDs and 14 partial remissions (PR) were recorded. Median survival time in this group was 13 months (range: 3-59+ months). In general, the group of patients treated with radical or subtotal surgery and the group of patients included in neurologic classes I-II and with performance status (PS) > or = 70 had a longer survival. In our experience, patients with grade III and IV astrocytoma receiving treatments similar to those described above showed no difference in survival and response. Regardless of treatment, none of the patients experienced severe toxicity.

[Unknown primary bone metastasis: therapeutic and diagnostic strategies]. / Metastasi ossee con partenza sconosciuta: strategie terapeutiche e diagnostiche.

The primary site remains unknown in 0.5-15% of patients with multiple metastases. In 5-20% of these patients bone metastases are the first sign of disease. Survival after diagnosis ranges 2 to 6 months and 1-year survival is less than 25%. First of all, this paper reviews the current diagnostic and therapeutic approaches to patients with bone metastases from an unknown primary site and then reports the 10-year experience with radiotherapy at the Radiotherapy Division of the Centro di Riferimento Oncologico (Aviano) and of the Pordenone General Hospital in this patient population. Seventy-nine patients with bone metastases were evaluated. In 33 patients histology confirmed the original diagnosis and in 46 patients diagnosis was based on radiological and clinical findings. With respect to pain relief, differences in irradiated areas and in the ages of the patients were not significant. The patient's sex, however, did make a difference both to the degree of pain relief achieved and to survival (more favorable in women). To conclude, this paper suggests the diagnostic procedures necessary for the correct follow-up of patients with bone metastases from an unknown primary site.

Usefulness of immunoscintigraphy in the follow-up of surgically treated gastrointestinal carcinomas using 111In-labelled anti-CEA monoclonal antibodies.

Twenty-five patients treated surgically for gastrointestinal carcinomas (16 rectum-sigmoid colon, 6 colon, 3 stomach) were investigated by immunoscintigraphy (IS) using 111In-labelled anti-CEA antibody (mouse monoclonal F023C5) F(ab')2 fragments in order to visualize questionable abdominopelvic recurrences (excluding the liver). Fifteen (60%) patients showed a rise in serum CEA levels above 5 ng/ml. Planar scans and emission computed tomographic (ECT) imaging were carried out without reference to the results of computed tomographic (CT) scans and gastrointestinal endoscopic examinations done 1-2 weeks before IS. Final diagnoses were based on biopsies and autopsies (13 cases) or on follow-up findings over at least 2 years (12 cases). Sixteen patients had a final diagnosis of recurrent malignant disease in the extrahepatic abdomen or pelvis. Of these, six were correctly diagnosed by both IS and conventional diagnostic procedures, six by IS only and two by conventional methods only. Two tumour recurrences remained undetected by both diagnostic approaches. However, five tumour recurrences were detected by IS more than 4 months earlier than by any other diagnostic procedures performed during clinical follow-up. Of the nine disease-free patients (disregarding the liver) three were correctly identified by both IS and the other diagnostic methods, four by IS only and two by conventional diagnostic procedures only. Overall sensitivity (75%) and specificity (89%) of 111In-IS were higher than figures obtained using CT scanning and endoscopy (50% and 78% respectively). True positive IS was observed in 6/15 (40%) CEA seropositive patients and in 6/10 (60%) CEA seronegative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation therapy and conservative surgery for soft tissue sarcomas of the extremities, torso and head and neck.

Between May 1985 and July 1990, 45 patients (pts.) with primary (39) or recurrent (6) soft tissue sarcomas of the extremities (82%), torso (11%) and head and neck (7%) were treated with radiation therapy and conservative surgery. Seven pts. not amenable to conservative surgery underwent preoperative radiation therapy whereas 38 pts. underwent local excision and post-operative radiation therapy. Out of the 38 pts. managed by postoperative radiation, 24 (63%) showed negative surgical margins and 14 (37%) positive margins, their tumor being adjacent to vital structures. Preoperative radiation allowed conservative surgery in all 7 pts. with initially inoperable tumor; surgical margins were negative in 5 and positive in 2 pts. Twenty-six pts. (58%) had tumor greater than or equal to 5 cm (5-24) and 19 (42%) less than 5 cm (2.5-4.5) in diameter. High grade tumors (G2-G3) were reported in 41 pts. (90%). In pts. treated postoperatively the radiation dose was 64-66 Gy/32-33 fractions and the pts. treated preoperatively received a dose of 50 Gy/25 fractions. Median follow-up was 33 months and all pts. had a minimum follow-up of 12 months (12-72). Three pts. (6.5%) had local failure and 9 (20%) developed distant metastases with local tumor control. All distant metastases occurred in AJC stage IIIB, 9/18 (50%), with an increased frequency by tumor size. Overall local control and disease free survival rates at 5 years (product-limit method) were 93% and 73%, respectively. An evident decrease in disease-free survival rate (33%) was noted for stage IIIB pts.(ABSTRACT TRUNCATED AT 250 WORDS)