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

Br J Radiol. 2012 Feb 14.

Massaccesi M, Digesù C, Macchia G, Deodato F, Ciuffreda M, Cucci E, Caravatta L, Corrado G, Padula GD, De Vizia R, Cellini N, Valentini V, Sallustio G, Ferrandina G, Pacelli F, Morganti AG.

Radiotherapy Unit.

OBJECTIVE:
The aim of this study was to evaluate the role of bilateral mammography undertaken before adjuvant radiotherapy in patients with conservatively managed invasive carcinoma of the breast.Methods: Patients with invasive breast cancer referred to the Radiotherapy Department of the Catholic University in Campobasso, Italy, between March 2002 and September 2006 were retrospectively reviewed. Patients were referred to our facility from other local and regional hospitals where they received breast-conserving surgery and adjuvant chemotherapy. They presented to our department for post-operative whole-breast radiotherapy. All patients underwent physical examination and bilateral mammography prior to adjuvant irradiation.

RESULTS:
201 patients met the selection criteria as delineated. Of these 201 patients who underwent pre-radiotherapy mammography, 3 had suspicious findings on mammography. In 2 of those cases, the histopathological examination confirmed the presence of residual disease within the residual mammary gland. In one case, the pre-radiotherapy mammogram allowed for the detection of disease persistence which was not otherwise appreciated on physical exam. In the other case, the diagnostic imaging confirmed only the findings of the physical exam. In both cases of residual disease, the tumour was found elsewhere in the breast and not at the primary site. In one patient, the radiological re-assessment led to a false-positive result. No cases of contralateral synchronous breast cancer were observed. The overall adjunctive cost of this strategy including a routine mammography besides the clinical visit was €7012 for all patients.

CONCLUSIONS:
No clear recommendation exists regarding post-operative mammography before adjuvant radiotherapy. In our experience, this strategy allowed for the detection of gross disease persistence after surgery which was not appreciated at clinical examination in 1 case out of 201. In this patient, adjuvant radiotherapy up to a total dose of 50?Gy would have been inadequate. Given the low cost of mammography, further investigation about its role in pre-radiotherapy evaluation are warranted.

Quality of life and toxicity of stereotactic radiotherapy in pancreatic tumors: a case series.

Cancer Invest. 2011 Feb;30(2):149-55.

Macchia G, Morganti AG, Cilla S, Ippolito E, Massaccesi M, Picardi V, Mattiucci GC, Bonomo P, Tambaro R, Pacelli F, Piermattei A, De Spirito M, Valentini V, Cellini N, Deodato F.

Radiotherapy Unit, Fondazione di Ricerca e Cura Giovanni Paolo II, Università-Cattolica, Campobasso, Italy.

AIM:
To analyze the results of extracranial stereotactic radiotherapy (ESRT) experience in pancreatic cancer patients.

METHODS:
Four noncoplanar fixed beams were used in all patients.

RESULTS:
Analysis of 16 patients was carried out. Overall response rate was 56.2%. Fifteen patients experienced local and/or distant progression of disease (median follow-up: 24 months). Two-year local progression-free, distant progression-free, and overall survivals were 85.7%, 58.7%, and 50.0%, respectively. Toxicity was less than grade 2 in all, although 1 patient had severe duodenal bleeding. Quality of life scores were unchanged.

CONCLUSIONS:
ESRT was associated with low complication rate, and not worsening the patients’ quality of life.

Douglas peritonectomy compared to recto-sigmoid resection in optimally cytoreduced advanced ovarian cancer patients: analysis of morbidity and oncological outcome.

Eur J Surg Oncol. 2011 Dec;37(12):1085-92. Epub 2011 Sep 25.

Gallotta V, Fanfani F, Vizzielli G, Panico G, Rossitto C, Gagliardi ML, Margariti PA, Salerno MG, Zannoni GF, Pacelli F, Scambia G, Fagotti A.

Department of Gynecologic Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.

BACKGROUND:
Rectosigmoidectomy (RR) with primary anastomosis or pelvic peritonectomy (PP) are often part of an optimal en bloc tumor resection in advanced ovarian cancer (AOC) patients with contiguous extension to or encasement of the reproductive organs, peritoneum of the cul-de-sac and sigmoid colon. We report our experience with two different surgical approaches in optimally cytoreduced AOC patients evaluating oncologic outcome and surgically associated morbidities.

METHODS:
Data from all consecutive AOC patients undergoing PP or RR as part of the surgical procedure during primary cytoreduction from 2004 through 2009 were extrapolated and analyzed using the chi-squared test, Cox proportional hazard model and Kaplan-Meier method including log-rank test.

RESULTS:
During the study period, we identified 187 AOC patients, fitting the inclusion criteria: 71 (38%) were submitted to RR and 116 (62%) were managed with PP. The estimated mean disease-free survival (DFS) was 30.7 months (95% CI 24.6-36.8) in the RR arm vs. 25.9 months in the PP arm (95% CI 21.9-29.9) (p 0.299); similarly, the estimated mean overall survival (OS) was 38.8 months (95% CI 33.4-44.2) in the RR arm and 48.2 months in the PP arm (95% CI 43.1-53.3) (p = 0.122). No statistically significant differences were found in terms of DFS and OS according to the mesocolic lymphnode status (p = 0.65 and p = 0.81, respectively).

CONCLUSIONS:
In conclusion, the current study clearly supports evidence that survival rates are similar for patients who achieved optimal residual tumor (RT), independent to whether they had RR or PP.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Malnutrition and postoperative complications in abdominal surgery.

Ann Surg. 2011 Oct;254(4):666; author reply 666-7.

Rosa F, Bossola M, Pacelli F, Alfieri S, Doglietto GB.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

Acta Oncol. 2011 Nov;50(8):1151-7. Epub 2011 Aug 18.

Caravatta L, Padula GD, Picardi V, Macchia G, Deodato F, Massaccesi M, Sofo L, Pacelli F, Rotondi F, Cecere G, Sallustio G, Di Lullo L, Piscopo A, Mignogna S, Bonomo P, Cellini N, Valentini V, Morganti AG.

Radiation Oncology Department, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.

BACKGROUND:
An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy.

MATERIAL AND METHODS:
A Phase II study was designed and clinical stage T3-T4 and/ or N ? 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan’s design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria.

RESULTS:
Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively.

CONCLUSIONS:
An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Validation of the new AJCC TNM staging system for gastric cancer in a large cohort of patients (n = 2,155): focus on the T category.

Eur J Surg Oncol. 2011 Sep;37(9):779-85. Epub 2011 Jul 2.

Marchet A, Mocellin S, Ambrosi A, Morgagni P, Vittimberga G, Roviello F, Marrelli D, de Manzoni G, Minicozzi A, Coniglio A, Tiberio G, Pacelli F, Rosa F, Nitti D.

Clinica Chirurgica II, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy.

BACKGROUND:
The prognostic value of T subclassification in patients with gastric carcinoma has been just implemented in the new AJCC TNM staging system, which has reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the present study was to validate the prognostic significance of the new T categorization within the frame of the latest TNM staging system.

METHODS:
We retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects who underwent radical resection for gastric carcinoma at six Italian centers from 1988 through 2006.

RESULTS:
Upon multivariate analysis, the new T categories, extent of lymph node dissection (D) and patient’s age were retained by the survival model as independent prognostic factors. In particular, the death risk for patients with T3 tumors was higher than that of patients with T2 tumors (HR: 1.42, P = 0.005). Among the 686 patients previously classified as having T2 tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%), respectively. After a median follow-up of 55 months, the 5-year overall survival rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P < 0.001). The survival advantage for the T2 as compared to T3 category was maintained even when N0 and N+ patients were separately considered (P = 0.0154 and P < 0.001, respectively).

CONCLUSIONS:
Our data confirm the prognostic difference between the newly proposed T2 and T3 categories, which should be implemented in the routine clinical practice to improve risk stratification of patients with gastric cancer.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Gastric linitis plastica: which role for surgical resection?

Gastric Cancer. 2012 Jan;15(1):56-60. Epub 2011 Jun 30.

Pedrazzani C, Marrelli D, Pacelli F, Di Cosmo M, Mura G, Bettarini F, Rosa F, de Manzoni G, Roviello F.

Unit of Surgical Oncology, Department of Human Pathology and Oncology, Istituto Toscano Tumouri, University of Siena and ITT, Siena, Italy.

BACKGROUND:
The role of surgery for gastric linitis plastica (GLP) is questioned. This study aimed to analyze our experience in the surgical treatment of GLP with specific reference to the resectability rate, prognosis, and mode of recurrence.

METHODS:
Results of surgery were analyzed in 102 patients with GLP.

RESULTS:
Of the 102 patients, 92 underwent surgical exploration, with resection performed in 60 cases. R2 resection was carried out in 20 patients and R1 in 12 patients, while the resection was considered potentially curative (R0) in 28 (27.5%). Overall, the median (95% confidence interval [CI]) survival time was 5.7 (3.7-7.5) months, with none of the patients alive at the end date of the study. For R0 patients the median (95% CI) survival time was 15.8 (11-20.7) months. The great majority of recurrences were intra-abdominal (peritoneal and/or locoregional), with a systemic component of the relapse that was rarely observed (5 cases).

CONCLUSIONS:
After primary surgery, GLP showed a poor prognosis without regard to the extent or type of resection. The failure of surgical treatment related mainly to the peritoneal spread of the disease. Specifically designed multimodality treatment protocols should be tested in this setting.

Gastrointestinal stromal tumors

Ann Ital Chir. 2011 Mar-Apr;82(2):97-109.

Ridolfini MP, Cassano A, Ricci R, Rotondi F, Berardi S, Cusumano G, Pacelli F, Doglietto GB.

Dipartimento di Chirurgia Oncologica, Università Cattolica del Sacro Cuore, Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche Giovanni Paolo II, Campobasso.

Gastrointestinal stromal tumor (GIST) account for 1% of all gastrointestinal neoplasms and are the most common mesenchymal tumor of gastrointestinal tract. There are considered to originate fom the intestinal cell of Cajal, an intestinal pacemaker cell, characterized usually express the KIT protein on immunohistochemistry. The stomach (40-60%) and small intestine (30-40%) are the most common locations. Diagnosis of these tumors is difficult to establish, because symptoms are vague and traditional diagnostic tests are not specific. GISTs shows a wide variety of clinical behaviours ranging fom benign to frankly malignant, making the outcome totally unpredictable. Surgery is the standard treatment of local GIST while Imatinib (tyrosine kinasi inhibitor) is considered as the standard treatment of metastatic disease. Resistence to Imatinib is also becoming a major clinical problem but new tirosyne kinase inibitor are being studied to improve the treatment and survival. The present paper is a review of the salient features of epidemiology, pathophysiology, diagnosis, therapy and prognostic factors of GIST

Changing clinical and pathological features of gastric cancer over time.

Br J Surg. 2011 Sep;98(9):1273-83. doi: 10.1002/bjs.7528. Epub 2011 May 10.

Marrelli D, Pedrazzani C, Morgagni P, de Manzoni G, Pacelli F, Coniglio A, Marchet A, Saragoni L, Giacopuzzi S, Roviello F; Italian Research Group for Gastric Cancer.

Department of Human Pathology and Oncology, Section of Surgical Oncology, University of Siena, Siena, Italy.

BACKGROUND:
The aim of the present multicentre observational study was to evaluate potential changes in clinical and pathological features of patients with gastric cancer (GC) treated in a 15-year interval.

METHODS:
A centralized prospective database including clinical, surgical, pathological and follow-up data from 2822 patients who had resection of a primary GC was analysed. The analysis focused on three periods: 1991-1995 (period 1), 1996-2000 (period 2) and 2001-2005 (period 3). Surgical procedure, pathological classification and follow-up were standardized among centres.

RESULTS:
The number of resections decreased from 1024 in period 1 to 955 and 843 in periods 2 and 3 respectively. More advanced stages and a smaller number of intestinal-type tumours of the distal third were observed over time. Five-year survival rates after R0 resection (2320 patients) did not change over time (overall: 56·6 and 51·2 per cent in periods 1 and 3; disease-free: 66·8 and 61·1 per cent respectively). Decreases in survival in more recent years were related particularly to more advanced stage, distal tumours and tumours in women. Multivariable analysis showed a lower probability of overall and disease-free survival in the most recent interval: hazard ratio 1·22 (95 per cent confidence interval 1·06 to 1·40) and 1·29 (1·06 to 1·58) respectively compared with period 1. Recurrent tumours were more frequently peritoneal rather than locoregional.

CONCLUSIONS:
Overall and disease-free survival rates after R0 resection of GC were unchanged over time.

Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Neoadjuvant Accelerated Concomitant Boost Radiotherapy and Multidrug Chemotherapy in Locally Advanced Rectal Cancer: A Dose-Escalation Study.

Am J Clin Oncol. 2011 May 6.

Caravatta L, Picardi V, Tambaro R, Padula GD, Macchia G, Deodato F, Massaccesi M, Pacelli F, Berardi S, Ridolfini MP, Di Filippo L, Fabrizio G, Ingrosso M, Cellini N, Valentini V, Morganti AG.

Departments of Radiation Oncology, Palliative Therapies, Surgery, Endoscopy, “John Paul II” Center for High Technology Reserch and Education in Biomedical Sciences, Catholic University
Pathology Unit, A. Cardarelli General Hospital
Surgery Unit, “Vietri” General Hospital, Larino, Campobasso
Department of Radiotherapy, Policlinico Universitario “A. Gemelli,” Catholic University, Rome, Italy
Department of Radiation Oncology, The Lacks Cancer Center Saint Mary’s Health Care, Grand Rapids, MI.

OBJECTIVES:
To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients.

METHODS:
Patients with cT3-T4 and/or cN?1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ?3 toxicity according to the Radiation Therapy Oncology Group criteria.

RESULTS:
Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level.

CONCLUSIONS:
An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.