The impact of the multidisciplinary tumor board (MDTB) on the management of pancreatic diseases in a tertiary referral center.

BACKGROUND: The implementation of multidisciplinary tumor board (MDTB) meetings significantly ameliorated the management of oncological diseases. However, few evidences are currently present on their impact on pancreatic cancer (PC) management. The aim of this study was to evaluate the impact of the MDTB on PC diagnosis, resectability and tumor response to oncological treatment compared with indications before discussion. PATIENTS AND METHODS: All patients with a suspected or proven diagnosis of PC presented at the MDTB from 2017 to 2019 were included in the study. Changes of diagnosis, resectability and tumor response to oncological/radiation treatment between pre- and post-MDTB discussion were analyzed. RESULTS: A total of 438 cases were included in the study: 249 (56.8%) were presented as new diagnoses, 148 (33.8%) for resectability assessment and 41 (9.4%) for tumor response evaluation to oncological treatment. MDTB discussion led to a change in diagnosis in 54/249 cases (21.7%), with a consequent treatment strategy variation in 36 cases (14.5%). Change in resectability was documented in 44/148 cases (29.7%), with the highest discrepancy for borderline lesions. The treatment strategy was thus modified in 27 patients (18.2%). The MDTB brought a modification in the tumor response assessment in 6/41 cases (14.6%), with a consequent protocol modification in four (9.8%) cases. CONCLUSIONS: MDTB discussion significantly impacts on PC management, especially in high-volume centers, with consistent variations in terms of diagnosis, resectability and tumor response assessment compared with indications before discussion.

Spatially fractionated radiotherapy (SFRT) targeting the hypoxic tumor segment for the intentional induction of non-targeted effects: An in silico study to exploit a new treatment paradigm.

INTRODUCTION: The possibility of intentionally triggering non targeted effects (NTEs) using spatially fractionated radiotherapy (SFRT) alone or combined with immunotherapy is an intriguing and fascinating area of research. Among different techniques for SFRT, stereotactic body radiotherapy targeting exclusively the central hypoxic segment of bulky tumors, (SBRT-PATHY) might trigger immunogenic cell death more efficiently. This in silico study aims to identify the best possible dosimetric trade-off for prescribing SFRT with volumetric modulated arc (VMAT) based stereotactic radiotherapy (SRT). MATERIAL AND METHODS: Eight spherical volumes defined "Gross Tumor Volumes" (GTVs) were generated with diameters of 3-10 cm (with incremental steps of 1 cm), simulating tumor lesions. The inner third part of each GTV (GTVcentral) was selected to simulate the central hypoxic area and a ring structure was derived around it to simulate the tumor periphery (GTVperipheral). Volumetric modulated arc radiation treatment (VMAT) plans were calculated to deliver a single fraction of 10 Gy to each GTVcentral with different dose prescription methods: target mean and isodose driven (40, 50, 60, 70, 80 and 90%).The volume of GTVperipheral receiving less than 2 Gy was recorded as dosimetric performance indicator. RESULTS: 56 possible dosimetric scenarios were analyzed. The largest percentage of GTVperipheral spared from the dose of 2 Gy was achieved with dose prescription methods to the 70% isodose line for lesions smaller than 6 cm (range 42.9-48.4%) and to the target mean for larger ones (range 52.9-64.5%). CONCLUSIONS: Optimizing the dose prescription method may reduce the dose to tumor periphery in VMAT-based SFRT, thus potentially sparing tumor infiltrating immune cells. The optimal method may vary according to the size of the lesion. This should be taken into account when designing prospective trials using SFRT.

PRODIGE: PRediction models in prOstate cancer for personalized meDIcine challenGE.

AIM: Identifying the best care for a patient can be extremely challenging. To support the creation of multifactorial Decision Support Systems (DSSs), we propose an Umbrella Protocol, focusing on prostate cancer. MATERIALS & METHODS: The PRODIGE project consisted of a workflow for standardizing data, and procedures, to create a consistent dataset useful to elaborate DSSs. Techniques from classical statistics and machine learning will be adopted. The general protocol accepted by our Ethical Committee can be downloaded from cancerdata.org . RESULTS: A standardized knowledge sharing process has been implemented by using a semi-formal ontology for the representation of relevant clinical variables. CONCLUSION: The development of DSSs, based on standardized knowledge, could be a tool to achieve a personalized decision-making.

Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2).

AIMS: To present the interim results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumours in different extracranial sites. MATERIALS AND METHODS: Patients were enrolled in different arms according to tumour site and clinical stage, and sequentially assigned to a given dose level. Acute toxicity, tumour response and early local control were investigated and reported. RESULTS: One hundred lesions in 65 consecutive patients (male/female: 30/35, median age: 66 years; range: 40-89) were treated. Of these 100 lesions, 21 were primary or metastatic lung tumours, 24 were liver metastases, 30 were bone metastases, 24 were nodal metastases and one was a primary vulvar melanoma. The prescribed dose ranged from 12 (BED(2Gy,α/ß:10) = 26.4 Gy) to 28 Gy (BED(2Gy,α/ß:10) = 106.4 Gy) to the planning target volume. Twenty-one patients (32.3%) experienced grade 1-2 acute toxicity, which was grade 2 in only two cases. The overall response rate based on computed tomography/magnetic resonance imaging was 52% (95% confidence interval 40.1-63.2%) and based on positron emission tomography scan was 90% (95% confidence interval 76.2-96.4%). As of November 2013, the median duration of follow-up was 11 months (range = 1-38). Recurrence/progression within the SRS-VMAT treated field was observed in nine patients (total lesions = 18): the inside SRS-VMAT field local control expressed on a per lesion basis was 87.8% at 12 months and 71.9% at 24 months. CONCLUSIONS: The maximum tolerable dose has not yet been reached in any study arm. SRS-VMAT resulted in positive early clinical results in terms of tumour response, local control rate and acute toxicity.

Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for glioblastoma. Hypotheses based on two prospective phase II trials.

AIM: To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM). PATIENTS AND METHODS: From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m(2)/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m(2)) was administered for 5 days every 28 days. RESULTS: Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens. CONCLUSION: Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule.

Intraluminal brachytherapy without stenting in intrahepatic papillary cholangiocarcinoma: a case report.

A 46-year-old female patient, with mild cholestasis by a large papillary cholangiocarcinoma involving the left hepatic duct, received intraluminal brachytherapy (50 Gy at 1 cm from the source axis) with the aim to relieve biliary obstruction without stent positioning. The patient presented with haemobilia and vegetant lesions in the left main biliary duct, and thus she had a high risk of early stent obstruction. Eighteen months after the treatment the patient presented tumour progression in the controlateral hepatic lobe, but had a patent left hepatic duct, without signs of cholestasis and/or cholangitis. Based on this and other published reports, intraluminal brachytherapy may be tested in a setting different from standard setting with the aim to safely palliate jaundice in patients with intraductal tumour growth in the biliary tract.

Head and neck cancer: new trends in research and clinical practice.

Head and neck cancer represents an interesting subject of research in the third millennium. Apart from basic research (molecular biology, genic therapies etc.) which it shares with other neoplasms, a number of studies are in progress in the field of clinical research. In particular trials of combined radiation and chemotherapy with one or several drugs are being carried out and they will certainly provide definitive results in the field of clinical application. Further acquisitions will be provided by the studies on non conventional dose fractionation and the application of intensity modulated radiotherapy. Finally, the first studies on chemoprevention in patients with malignant or precancerous lesions of the head and neck will be soon concluded.

Research trends in the treatment of prostatic neoplasms.

Prostatic carcinoma, in the male population ranks first as incidence and second as cause of oncologic mortality. In the last decades, significantly better clinical results were achieved both in diagnosis and therapy. The latter covers a broad range of possibilities, including standard surgery, nerve-sparing surgery, combined surgery and hormonotherapy, cryosurgery, external beam radiotherapy, brachytherapy, conformal radiotherapy, combined hormone and radiation therapy, as well as conventional hormonotherapy. However, there is still much controversy on the role of the screening, the most appropriate staging modalities, the most adequate treatment in the various presentations of the disease. The present trends of the clinical research in this field are directed towards the identification of factors involved in the onset of this neoplasm and the possibility of decreasing its incidence with programs of chemoprevention, the identification of new biological markers able to assess the biological potential of the disease, the comparison between the main treatment modalities of localized carcinoma (surgery, brachytherapy, external beam radiotherapy) and the definition of parameters predictive of the response to the various treatments to better personalize the therapy of the single patient, the development of treatments based on genetic therapy and of effective systemic therapies able to control the hormone-resistant advanced disease and to clarify the impact of the different therapies on the quality of life and health care costs.

Economic and organizational aspects in the management of prostate cancer.

In the last decade a rapid increase in the incidence of prostate cancer was observed. The reasons for this increase are associated to the progressive population aging, especially in the developed countries as well as to the growing number of identified cases with the widespread use of prostate specific antigen. A number of aspects of the disease are still to be considered in depth: the natural history of the disease in patients with early diagnosis, the potential costs of screening programs in financial, social and psychologic terms, the effectiveness and especially cost-effectiveness of different treatments and follow-up for local and advanced forms. Because of the long natural history of prostate cancer and the effectiveness of hormonal treatments used as salvage after failure of primary therapy, the differences in survival among the various therapeutic options, from radical prostatectomy to radiotherapy, or simple clinical control in selected cases are probably minor. This is the reason why future clinical studies should necessarily be based on multidimensional evaluations, taking into account the clinical outcome as well as the quality of life and costs of the different treatment modalities examined.

Cost- and time-sparing simplified conformal therapy for prostate cancer: is it feasible?

PURPOSE: It was hypothesized that using a simplified technique of volumes profiles determination (STVPD) based on CT data sets (correlate and projection) would increase the target dose without increasing the bladder and rectal dose obtained by conventional simulation techniques. To test this hypothesis, patients referred for radical radiation treatment for prostate carcinoma were prospectively evaluated by performing treatment planning using standard simulation, with (SSB) and without corner blocks (SSWB), STVPD, and 3D beam's eye view. METHODS AND MATERIALS: Twenty-one patients with prostate carcinoma (stage B: 7; stage C: 14) underwent four treatment planning procedures where the field arrangement was defined by standard simulation (SSB and SSWB), STVPD, and 3D beam's eye view (BEV) with a four field (10 MV photons) box technique. Dose-volume histograms (DVHs) for the planning target volume (PTV), bladder, and rectum (relatives to the four techniques) were generated for all patients and compared; average percentage dose to the bladder and rectum were also calculated. RESULTS: STVPD and 3D BEV treated an increased percentage of PTV at 95% isodose level, in comparison to standard simulation (with and without blocks). No statistically significant differences were found between the two techniques. A significant reduction of irradiated bladder volume was found between 3D BEV and STVPD versus simulation with and without blocks (mean percentage dose: 77.3%, 81.8%, 93.5%, and 92.6% respectively). No marked differences were recorded in rectal irradiation (mean percentage dose: 53.1%, 53.7%, 51.9%, and 50.2% respectively). Time required for treatment planning (excluding CT scan and definitive simulation) was less than 15 minutes for STVPD and more than 120 minutes for 3D BEV. CONCLUSION: Our results confirm the inadequacy of standard simulation. It is possible, with conformal therapy, to increase the dose to the PTV, decreasing the irradiated volume of the bladder. The absence of sparing effect in the rectum is discussed. Using a box technique, STVPD can be used routinely to define the PTV in patients with prostate cancer, reducing the time required for treatment planning, with dosimetric results similar to those of 3D BEV.

Radiotherapy, local control and survival in brain tumors.

High grade glial brain tumors and brain metastases are a complex subject with still unsatisfactory therapeutic results for the frequent absence of early and precise diagnosis as well as for the limited therapeutic interval between the tumor and presumed healthy tissues. The therapeutic problems of cellular hypoxia, the rapid recovery of sublethal damage for neoplastic cells, the rapid regrowth, have led to a number of efforts to deliver the dose of radiotherapy in various associations. The constant technological trend to increase the high dose gradient to the peripheral tumor, is reported.

Organ preservation in the management of prostatic cancer.

Thirty-two patients with cT2 prostatic adenocarcinoma underwent a protocol of combined treatment based on: neoadjuvant hormonotherapy (LH-RH analogues + antiandrogens) and concomitant external radiotherapy (ERT), two months before ERT until the end of it; ERT to the entire pelvis (45 Gy) with a boost dose to the prostatic volume (+20 Gy). All patients completed the planned treatment. Acute toxicity was moderate (Gr 1-2 RTOG). At a median follow-up of 22 months (range: 6-68) one patient (3.1%) showed bone metastases while none had local disease progression. Overall 5 year survival and disease-free survival were 100% and 97% respectively. Late toxicity was mild (Gr 1 RTOG: intestinal: 3.1%; urological: 21.9%). The protocol was shown to be feasible with no relevant toxicity. Even if the follow-up was short, results achieved in this group of potentially resectable prostatic cancer patients seem to confirm the possibility of achieving results comparable to those of surgery with no relevant impairment of urinary and intestinal function, thus with an acceptable quality of life.