To present a systematic review of techniques and clinical results. A systematic review of publish... more To present a systematic review of techniques and clinical results. A systematic review of published literature was performed. Only studies reporting patient outcome after radiosurgery (single fraction) delivered with robotic devices [i.e., robotic radiosurgery (RRS)] have been analyzed. A total of 96 patients from 5 studies were included. The studies are characterized by small series and different methods in terms of dose, target definition, combination with chemotherapy and/or standard fractionated radiotherapy and evaluation modalities. Preliminary results are positive in terms of tumor response (ORR = 56%) and local control of the tumor (crude rate of local progressions: 19.5%). Results for median overall survival (11.4 mo) seem comparable with the ones of prolonged chemoradiation (range: 8.6-13.0 mo). However, gastrointestinal toxicity seems to be the main limitation of RRS, especially at the duodenal level. RRS allows for local treatment in a shortened time (1 fraction) compared to traditional treatments (about 1 mo), providing the possibility for an easy integration with systemic therapies. Preliminary results did not show any outcome differences compared to standard chemoradiation. Thus, further efforts to reduce gastrointestinal toxicity are strongly needed.
No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. ... more No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. In the present study, a nationwide survey using a questionnaire was performed to enquire the local standards for PC diagnosis and radiotherapy treatment. Fifty-seven percent of 140 Italian centres completed questionnaire. The main causes of no radiotherapy indication were poor general condition (45%) and lack of guidelines (25%). Physicians (38%) employed neoadjuvant therapy in locally advanced PC patients, while in other centres (62%) adjuvant chemoradiation was administered. Adjuvant gemcitabine-based chemotherapy was selected as the treatment of choice by 59% of centres. Patients were treated mostly with doses of 50-54.9 Gy on the tumour (or bed) plus lymph nodes. A 3D-CRT technique was used in 81.2% of centres, while IMRT and IGRT were available in 61.2 and 48.7% of cases, respectively. Extensive variation exists with regard to patterns of care for PC in Italy. Nevertheless, cooperative studies emerging from this survey appeared beneficial.
In 2003, at time of trial design, the role of adjuvant therapy in PA was debated and no recommend... more In 2003, at time of trial design, the role of adjuvant therapy in PA was debated and no recommended standard existed. Since in stage III and IV pancreatic adenocarcinoma (PA), PEFG regimen significantly improved progression-free survival and overall survival (OS) as compared with gemcitabine (G), we assessed the impact upon disease control of PEFG regimen and G in the adjuvant setting as well. Material and Methods: After R0 or R1 resection for PA, patients with stage IB-III disease, aged 18−70 years, Karnofsky performance status (PS) >60 were randomized within 8 weeks from surgery to receive either G 1 g/m 2 /weekly Q3 every 4 weeks (Arm A), or PEFG (cisplatin and epirubicin at 40 mg/m 2 each on day one, gemcitabine at 600 mg/m 2 on days 1 and 8 and 5-FU at 200 mg/m 2 /day on days 1 to 28) every 4 weeks (Arm B). In both arms chemotherapy was administered for 3 months and followed by radiotherapy (54−60 Gy in 27−30 fractions) with concurrent 5-FU 250 mg/m 2 /day. The primary endpoint was the probability of being disease-free at 1 year (DFS 1 y) from surgery. The Fleming design was used to calculate the sample size. Assuming P0 = 35% and P1 = 55%, a?.05 and b.10, the study was to enroll 51 patients per arm. The treatment regimen had to be considered of interest with >23 patients being DFS 1 y. Results: Between August 2003 and August 2008, 102 patients were enrolled, stratified by center and resection margin and randomized (51 per arm). One arm B patient was ineligible due to metastatic disease, 1 arm A patient received PEFG regimen and 1 arm B patient withdrew consent. An intent-to-treat analysis on eligible patients was performed. Patients' characteristics were (A/B): median age 61/60, median PS 90/90, stage IB-IIA 25/15%; stage IIB 63/78%; stage III 12/7%; grade 3 29/46%; R1 35/29%; pre-and post-surgery surgery CA19.9 >upper limit of laboratory normal 69/81% and 29/33%, tumor size >2.9 cm 44/42%. To date, 50 A and 48 B patients are assessable for the primary endpoint: 23 (46%) and 31 (65%) patients were DFS 1 y. Main G3−4 toxicity was: neutropenia in 15/58% and thrombocytopenia in 0/11% of cycles. Conclusion: This is the first randomized trial on single agent or combination chemotherapy as adjuvant treatment of PA. With a mature follow-up for 98% of patients, PEFG fulfilled the primary endpoint and warrants further study while G not yet.
Prostate cancer is a heterogeneous, indolent or sometimes aggressive tumor. Treatment options are... more Prostate cancer is a heterogeneous, indolent or sometimes aggressive tumor. Treatment options are various and without proved superiority. Radiotherapy (RT) plays a key role in the disease history. Technological evolution with Intensity Modulate Radiation Therapy (IMRT) and Image Guided Radiation Therapy (IGRT) allowed improvement, with significant results on local control and survival. Hypofractionation, Stereotactic Body RT (SBRT) and new brachytherapy approachs are still under investigation, with promising opportunities. Adjuvant vs salvage postoperative RT, hormone association, prophylactic pelvic irradiation are still under debate, but guidelines express overlapping indications. Multidisciplinary managements will be the future for care optimization, providing the best tool for holistic and informed patients’ choice.
The natural history and survival of breast cancer are extremely variable although the advances an... more The natural history and survival of breast cancer are extremely variable although the advances and improvement in treatment in recent years led to a lower mortality. In fact, in spite of the administration of systemic adjuvant therapy, women with metastatic lymph nodes at diagnosis have a risk of disease progression at 5 years of 40-50%. The disease heterogeneity and the intrinsic tumor cell resistance to therapies are determining factors of the problem. The role of parameters as tumor size, grading, vascular spread, axillary lymph node status, are well defined. However the increasingly early diagnosis and changes in clinical practice have led to the need for non morphologic parameters as estrogen and progesteron receptors, cell proliferation index, labelling index, growth factors tumor-dependent genes (p53, HER2), cell cycle regulators (cyclins). Specific cellular and molecular alterations are studied to identify diagnosticoinstrumental images (MRI) of tumor angiogenesis, the cause...
To determine the recommended dose of endoscopically assisted high-dose-rate intraluminal brachyth... more To determine the recommended dose of endoscopically assisted high-dose-rate intraluminal brachytherapy (HDR-192Ir-ILBT) as a palliative treatment of extrahepatic biliary tract cancer. Patients with non-metastatic extrahepatic biliary cancer with age <80 years, unsuitable for surgical resection or radiochemotherapy for comorbidities or Eastern Cooperative Oncology Group (ECOG) ≥2 or patients with age ≥80 years were included. They were undergone to implantation of metal stents by endoscopic retrograde cholangiopancreatography followed by HDR-192Ir-ILBT. The initial dose of HDR-192-Ir-ILBT was 15 Gy. Three levels of dose were planned. At each dose level almost three patients were treated, and if no Grade 3-4 toxicity (considering as dose-limiting toxicity) was recorded, dose escalation was applied with 5 Gy increments until the maximum tolerated dose was established. A high dose Iridium-192 after loading system was used (Nucletron Microselectron HDR). From May 2007 to January 2010, ...
The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups o... more 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. 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. 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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. 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.
To evaluate the preliminary results of perioperative endoscopy-guided brachytherapy (BT) in recur... more To evaluate the preliminary results of perioperative endoscopy-guided brachytherapy (BT) in recurrent sinonasal and nasopharyngeal tumors already treated for their primary tumor with a full course of radiotherapy. Patients with recurrence and already treated with a previous full course of radiotherapy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;65 Gy who underwent BT from December 2010 to January 2014 were taken into account for this work. Macroscopic disease was resected by an endoscopic approach, and catheters for BT were endoscopically positioned and fixed at the same time on the surgical bed. Surgery was performed under electromagnetic navigation guidance. The irradiation dose was 30 Gy in 12 fractions, 2.5 Gy each, twice a day, in 6 days. We performed the endoscopy-guided BT 11 times in 9 patients; in two cases, no previous radiation therapy had been performed; and in one case, followup was too short to be considered. A total of 6 patients were eligible for the analysis. One patient underwent BT three times because of previous target margin recurrences. There were no immediate complications. The median and mean followups were 21 and 19 months, respectively. The median V90 and V85% were 93% and 95%, respectively. In one case, we had a transient deficit of the VI cranial nerve (G3), and in another case, we diagnosed a noncomplicated osteonecrosis (G2). The median disease-free survival is 12 months, and the median overall survival is 23 months. The combination of endoscopy and BT seems to be a safe option for treating recurrent sinonasal and nasopharyngeal tumors.
Background and purpose: A systematic review and meta-analysis was performed to assess the impact ... more Background and purpose: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3-and 5-year survival in patients with resectable gastric cancer. Methods: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score. Results: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT = 17) and 1.31 (95% CI: 1.04-1.66; NNT = 13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found. Conclusion: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.
Background and purpose: Three-dimensional conformal radiotherapy and intensity modulated radiothe... more 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.
The article reports a feasibility study about the potentiality of an in vivo dosimetry method for... more The article reports a feasibility study about the potentiality of an in vivo dosimetry method for the adaptive radiotherapy of the lung tumors treated by 3D conformal radiotherapy techniques (3D CRTs). At the moment image guided radiotherapy (IGRT) has been used for this aim, but it requires taking many periodic radiological images during the treatment that increase workload and patient dose. In vivo dosimetry reported here can reduce the above efforts, alerting the medical staff for the commissioning of new radiological images for an eventual adaptive plan. The in vivo dosimetry method applied on 20 patients makes use of the transit signal St on the beam central axis measured by a small ion chamber positioned on an electronic portal imaging device (EPID) or by the EPID itself. The reconstructed in vivo dosimetry at the isocenter point Diso requires a convolution between the transit signal St and a dose reconstruction factor C that essentially depends on (i) tissue inhomogeneities along the beam central axis and (ii) the in-patient isocenter depth. The C factors, one for every gantry angle, are obtained by processing the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s computed tomography scan. The method has been recently applied in some Italian centers to check the radiotherapy of pelvis, breast, head, and thorax treatments. In this work the dose reconstruction was carried out in five centers to check the Diso in the lung tumor during the 3D CRT, and the results have been used to detect the interfraction tumor anatomy variations that can require new CT imaging and an adaptive plan. In particular, in three centers a small ion chamber was positioned below the patient and used for the St measurement. In two centers, the St signal was obtained directly by 25 central pixels of an a-Si EPID, equipped with commercial software that enabled its use as a stable detector. A tolerance action level of +/- 6% for every checked beam was assumed. This means that when a difference greater than 6% between the predicted dose by the treatment planning system, Diso,TPS, and the Diso was observed, the clinical action started to detect possible errors. 60% of the patients examined presented morphological changes during the treatment that were checked by the in vivo dosimetry and successively confirmed by the new CT scans. In this work, a patient that showed for all beams Diso values outside the tolerance level, new CT scans were commissioned for an adaptive plan. The lung dose volume histograms (DVHs) for a Diso,TPs=2 Gy for fraction suggested the adaptive plan to reduce the dose in lung tissue. The results of this research show that the dose guided radiotherapy (DGRT) by the Diso reconstruction was feasible for daily or periodic investigation on morphological lung tumor changes. In other words, since during 3D CRT treatments the anatomical lung tumor changes occur frequently, the DGRT can be well integrated with the IGRT.
The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conform... more The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT.
To present a systematic review of techniques and clinical results. A systematic review of publish... more To present a systematic review of techniques and clinical results. A systematic review of published literature was performed. Only studies reporting patient outcome after radiosurgery (single fraction) delivered with robotic devices [i.e., robotic radiosurgery (RRS)] have been analyzed. A total of 96 patients from 5 studies were included. The studies are characterized by small series and different methods in terms of dose, target definition, combination with chemotherapy and/or standard fractionated radiotherapy and evaluation modalities. Preliminary results are positive in terms of tumor response (ORR = 56%) and local control of the tumor (crude rate of local progressions: 19.5%). Results for median overall survival (11.4 mo) seem comparable with the ones of prolonged chemoradiation (range: 8.6-13.0 mo). However, gastrointestinal toxicity seems to be the main limitation of RRS, especially at the duodenal level. RRS allows for local treatment in a shortened time (1 fraction) compared to traditional treatments (about 1 mo), providing the possibility for an easy integration with systemic therapies. Preliminary results did not show any outcome differences compared to standard chemoradiation. Thus, further efforts to reduce gastrointestinal toxicity are strongly needed.
No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. ... more No information is currently available regarding pancreatic cancer (PC) pattern of care in Italy. In the present study, a nationwide survey using a questionnaire was performed to enquire the local standards for PC diagnosis and radiotherapy treatment. Fifty-seven percent of 140 Italian centres completed questionnaire. The main causes of no radiotherapy indication were poor general condition (45%) and lack of guidelines (25%). Physicians (38%) employed neoadjuvant therapy in locally advanced PC patients, while in other centres (62%) adjuvant chemoradiation was administered. Adjuvant gemcitabine-based chemotherapy was selected as the treatment of choice by 59% of centres. Patients were treated mostly with doses of 50-54.9 Gy on the tumour (or bed) plus lymph nodes. A 3D-CRT technique was used in 81.2% of centres, while IMRT and IGRT were available in 61.2 and 48.7% of cases, respectively. Extensive variation exists with regard to patterns of care for PC in Italy. Nevertheless, cooperative studies emerging from this survey appeared beneficial.
In 2003, at time of trial design, the role of adjuvant therapy in PA was debated and no recommend... more In 2003, at time of trial design, the role of adjuvant therapy in PA was debated and no recommended standard existed. Since in stage III and IV pancreatic adenocarcinoma (PA), PEFG regimen significantly improved progression-free survival and overall survival (OS) as compared with gemcitabine (G), we assessed the impact upon disease control of PEFG regimen and G in the adjuvant setting as well. Material and Methods: After R0 or R1 resection for PA, patients with stage IB-III disease, aged 18−70 years, Karnofsky performance status (PS) >60 were randomized within 8 weeks from surgery to receive either G 1 g/m 2 /weekly Q3 every 4 weeks (Arm A), or PEFG (cisplatin and epirubicin at 40 mg/m 2 each on day one, gemcitabine at 600 mg/m 2 on days 1 and 8 and 5-FU at 200 mg/m 2 /day on days 1 to 28) every 4 weeks (Arm B). In both arms chemotherapy was administered for 3 months and followed by radiotherapy (54−60 Gy in 27−30 fractions) with concurrent 5-FU 250 mg/m 2 /day. The primary endpoint was the probability of being disease-free at 1 year (DFS 1 y) from surgery. The Fleming design was used to calculate the sample size. Assuming P0 = 35% and P1 = 55%, a?.05 and b.10, the study was to enroll 51 patients per arm. The treatment regimen had to be considered of interest with >23 patients being DFS 1 y. Results: Between August 2003 and August 2008, 102 patients were enrolled, stratified by center and resection margin and randomized (51 per arm). One arm B patient was ineligible due to metastatic disease, 1 arm A patient received PEFG regimen and 1 arm B patient withdrew consent. An intent-to-treat analysis on eligible patients was performed. Patients' characteristics were (A/B): median age 61/60, median PS 90/90, stage IB-IIA 25/15%; stage IIB 63/78%; stage III 12/7%; grade 3 29/46%; R1 35/29%; pre-and post-surgery surgery CA19.9 >upper limit of laboratory normal 69/81% and 29/33%, tumor size >2.9 cm 44/42%. To date, 50 A and 48 B patients are assessable for the primary endpoint: 23 (46%) and 31 (65%) patients were DFS 1 y. Main G3−4 toxicity was: neutropenia in 15/58% and thrombocytopenia in 0/11% of cycles. Conclusion: This is the first randomized trial on single agent or combination chemotherapy as adjuvant treatment of PA. With a mature follow-up for 98% of patients, PEFG fulfilled the primary endpoint and warrants further study while G not yet.
Prostate cancer is a heterogeneous, indolent or sometimes aggressive tumor. Treatment options are... more Prostate cancer is a heterogeneous, indolent or sometimes aggressive tumor. Treatment options are various and without proved superiority. Radiotherapy (RT) plays a key role in the disease history. Technological evolution with Intensity Modulate Radiation Therapy (IMRT) and Image Guided Radiation Therapy (IGRT) allowed improvement, with significant results on local control and survival. Hypofractionation, Stereotactic Body RT (SBRT) and new brachytherapy approachs are still under investigation, with promising opportunities. Adjuvant vs salvage postoperative RT, hormone association, prophylactic pelvic irradiation are still under debate, but guidelines express overlapping indications. Multidisciplinary managements will be the future for care optimization, providing the best tool for holistic and informed patients’ choice.
The natural history and survival of breast cancer are extremely variable although the advances an... more The natural history and survival of breast cancer are extremely variable although the advances and improvement in treatment in recent years led to a lower mortality. In fact, in spite of the administration of systemic adjuvant therapy, women with metastatic lymph nodes at diagnosis have a risk of disease progression at 5 years of 40-50%. The disease heterogeneity and the intrinsic tumor cell resistance to therapies are determining factors of the problem. The role of parameters as tumor size, grading, vascular spread, axillary lymph node status, are well defined. However the increasingly early diagnosis and changes in clinical practice have led to the need for non morphologic parameters as estrogen and progesteron receptors, cell proliferation index, labelling index, growth factors tumor-dependent genes (p53, HER2), cell cycle regulators (cyclins). Specific cellular and molecular alterations are studied to identify diagnosticoinstrumental images (MRI) of tumor angiogenesis, the cause...
To determine the recommended dose of endoscopically assisted high-dose-rate intraluminal brachyth... more To determine the recommended dose of endoscopically assisted high-dose-rate intraluminal brachytherapy (HDR-192Ir-ILBT) as a palliative treatment of extrahepatic biliary tract cancer. Patients with non-metastatic extrahepatic biliary cancer with age <80 years, unsuitable for surgical resection or radiochemotherapy for comorbidities or Eastern Cooperative Oncology Group (ECOG) ≥2 or patients with age ≥80 years were included. They were undergone to implantation of metal stents by endoscopic retrograde cholangiopancreatography followed by HDR-192Ir-ILBT. The initial dose of HDR-192-Ir-ILBT was 15 Gy. Three levels of dose were planned. At each dose level almost three patients were treated, and if no Grade 3-4 toxicity (considering as dose-limiting toxicity) was recorded, dose escalation was applied with 5 Gy increments until the maximum tolerated dose was established. A high dose Iridium-192 after loading system was used (Nucletron Microselectron HDR). From May 2007 to January 2010, ...
The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups o... more 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. 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. 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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. 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.
To evaluate the preliminary results of perioperative endoscopy-guided brachytherapy (BT) in recur... more To evaluate the preliminary results of perioperative endoscopy-guided brachytherapy (BT) in recurrent sinonasal and nasopharyngeal tumors already treated for their primary tumor with a full course of radiotherapy. Patients with recurrence and already treated with a previous full course of radiotherapy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;65 Gy who underwent BT from December 2010 to January 2014 were taken into account for this work. Macroscopic disease was resected by an endoscopic approach, and catheters for BT were endoscopically positioned and fixed at the same time on the surgical bed. Surgery was performed under electromagnetic navigation guidance. The irradiation dose was 30 Gy in 12 fractions, 2.5 Gy each, twice a day, in 6 days. We performed the endoscopy-guided BT 11 times in 9 patients; in two cases, no previous radiation therapy had been performed; and in one case, followup was too short to be considered. A total of 6 patients were eligible for the analysis. One patient underwent BT three times because of previous target margin recurrences. There were no immediate complications. The median and mean followups were 21 and 19 months, respectively. The median V90 and V85% were 93% and 95%, respectively. In one case, we had a transient deficit of the VI cranial nerve (G3), and in another case, we diagnosed a noncomplicated osteonecrosis (G2). The median disease-free survival is 12 months, and the median overall survival is 23 months. The combination of endoscopy and BT seems to be a safe option for treating recurrent sinonasal and nasopharyngeal tumors.
Background and purpose: A systematic review and meta-analysis was performed to assess the impact ... more Background and purpose: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3-and 5-year survival in patients with resectable gastric cancer. Methods: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score. Results: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT = 17) and 1.31 (95% CI: 1.04-1.66; NNT = 13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found. Conclusion: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.
Background and purpose: Three-dimensional conformal radiotherapy and intensity modulated radiothe... more 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.
The article reports a feasibility study about the potentiality of an in vivo dosimetry method for... more The article reports a feasibility study about the potentiality of an in vivo dosimetry method for the adaptive radiotherapy of the lung tumors treated by 3D conformal radiotherapy techniques (3D CRTs). At the moment image guided radiotherapy (IGRT) has been used for this aim, but it requires taking many periodic radiological images during the treatment that increase workload and patient dose. In vivo dosimetry reported here can reduce the above efforts, alerting the medical staff for the commissioning of new radiological images for an eventual adaptive plan. The in vivo dosimetry method applied on 20 patients makes use of the transit signal St on the beam central axis measured by a small ion chamber positioned on an electronic portal imaging device (EPID) or by the EPID itself. The reconstructed in vivo dosimetry at the isocenter point Diso requires a convolution between the transit signal St and a dose reconstruction factor C that essentially depends on (i) tissue inhomogeneities along the beam central axis and (ii) the in-patient isocenter depth. The C factors, one for every gantry angle, are obtained by processing the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s computed tomography scan. The method has been recently applied in some Italian centers to check the radiotherapy of pelvis, breast, head, and thorax treatments. In this work the dose reconstruction was carried out in five centers to check the Diso in the lung tumor during the 3D CRT, and the results have been used to detect the interfraction tumor anatomy variations that can require new CT imaging and an adaptive plan. In particular, in three centers a small ion chamber was positioned below the patient and used for the St measurement. In two centers, the St signal was obtained directly by 25 central pixels of an a-Si EPID, equipped with commercial software that enabled its use as a stable detector. A tolerance action level of +/- 6% for every checked beam was assumed. This means that when a difference greater than 6% between the predicted dose by the treatment planning system, Diso,TPS, and the Diso was observed, the clinical action started to detect possible errors. 60% of the patients examined presented morphological changes during the treatment that were checked by the in vivo dosimetry and successively confirmed by the new CT scans. In this work, a patient that showed for all beams Diso values outside the tolerance level, new CT scans were commissioned for an adaptive plan. The lung dose volume histograms (DVHs) for a Diso,TPs=2 Gy for fraction suggested the adaptive plan to reduce the dose in lung tissue. The results of this research show that the dose guided radiotherapy (DGRT) by the Diso reconstruction was feasible for daily or periodic investigation on morphological lung tumor changes. In other words, since during 3D CRT treatments the anatomical lung tumor changes occur frequently, the DGRT can be well integrated with the IGRT.
The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conform... more The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT.
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Papers by Gian Mattiucci