Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs.

INTRODUCTION: The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. METHODS AND MATERIALS: From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients. RESULTS: The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001). CONCLUSIONS: Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.

Early variation of 18-fluorine-labelled fluorodeoxyglucose PET-derived parameters after chemoradiotherapy as predictors of survival in locally advanced pancreatic carcinoma patients.

OBJECTIVE: To investigate if early variation of PET-derived parameters after concomitant chemoradiotherapy (CRT) predicts overall survival (OS), local relapse free survival (LRFS), distant relapse free survival (DRFS) and progression free survival (PFS) in locally advanced pancreatic cancer (LAPC) patients. METHODS: Fifty-two LAPC patients (median age: 61 years; range: 35-85) with available FDG PET/CT before and after RT (2-6 months, median: 2) were enrolled from May 2005 to June 2015. The predictive value of the percentage variation of mean/maximum standard uptake value (ΔSUVmean/max), metabolic tumour volume (ΔMTV) and total lesion glycolysis (ΔTLG), estimated considering different uptake thresholds (40-50-60%), was investigated between pre- and post-RT PET. The percentage difference between gastrointestinal cancer-associated antigen (ΔGICA) levels measured at the time of PET was also considered. Log-rank test and Cox regression analysis were performed to assess the prognostic value of considered PET-derived parameters on survival outcomes. RESULTS: The median follow-up was 13 months (range: 4-130). At univariate analysis, ΔTLG50 showed borderline significance in predicting OS (P = 0.05) and was the most significant parameter correlated to LRFS and PFS (P = 0.001). Median LRFS was 4 and 33 months if ΔTLG50 was below or above 35% respectively (P = 0.0003); similarly, median PFS was 3 vs 6 months (P = 0.0009). No significant correlation was found between PET-derived parameters and DRFS, while the ΔGICA was the only borderline significant prognostic value for this endpoint (P = 0.05). CONCLUSION: PET-derived parameters predict survival in LAPC patients; in particular, ΔTLG50 is the strongest predictor. The combination of these biochemical and imaging biomarkers is promising in identifying patients at higher risk of earlier relapse.

Multi-institutional evaluation of MVCT guided patient registration and dosimetric precision in total marrow irradiation: A global health initiative by the international consortium of total marrow irradiation.

PURPOSE: Total marrow irradiation (TMI) is a highly conformal treatment of the human skeleton structure requiring a high degree of precision and accuracy for treatment delivery. Although many centers worldwide initiated clinical studies using TMI, currently there is no standard for pretreatment patient setup. To this end, the accuracy of different patient setups was measured using pretreatment imaging. Their impact on dose delivery was assessed for multiple institutions. METHODS AND MATERIALS: Whole body imaging (WBI) or partial body imaging (PBI) was performed using pretreatment megavoltage computed tomography (MVCT) in a helical Tomotherapy machine. Rigid registration of MVCT and planning kilovoltage computed tomography images were performed to measure setup error and its effect on dose distribution. The entire skeleton was considered the planning target volume (PTV) with five sub regions: head/neck (HN), spine, shoulder and clavicle (SC), and one avoidance structure, the lungs. Sixty-eight total patients (>300 images) across six institutions were analyzed. RESULTS: Patient setup techniques differed between centers, creating variations in dose delivery. Registration accuracy varied by anatomical region and by imaging technique, with the lowest to the highest degree of pretreatment rigid shifts in the following order: spine, pelvis, HN, SC, and lungs. Mean fractional dose was affected in regions of high registration mismatch, in particular the lungs. CONCLUSIONS: MVCT imaging and whole body patient immobilization was essential for assessing treatment setup, allowing for the complete analysis of 3D dose distribution in the PTV and lungs (or avoidance structures).

Simultaneous tumour dose escalation and liver sparing in Stereotactic Body Radiation Therapy (SBRT) for liver tumours due to CTV-to-PTV margin reduction.

PURPOSE: To quantify potential benefits of CTV-to-PTV margin reduction for SBRT of liver tumours, as allowed by enhanced treatment precision. MATERIALS AND METHODS: For 14 patients plans were generated for the clinical margin and for 3 tighter margins. An in-house developed algorithm was used to optimise beam directions, shapes, and weights for generation of the plan with the highest isocenter dose (D(iso)), while keeping the minimum PTV dose at least 65%xD(iso) and strictly adhering to all imposed hard OAR constraints. Each plan contains 10 optimal beam directions, automatically selected from up to 252 coplanar and non-coplanar input directions. RESULTS: Apart from the expected tumour dose escalation (D(iso), EUD(PTV), gEUD(PTV)) with decreasing margin, a simultaneous improved sparing of the normal liver (D33%, D50%, D(mean)) was also observed. The smaller the margin was, the bigger both effects were. For renormalized plans with D(iso) equal to the clinical value (3x19.2Gy), and a margin reduction of 50% (2.5mm laterally, 5mm longitudinally), normal liver D33% and D50% reduced on average by 22% (maximum 38%), and 26% (maximum 47%), respectively. CONCLUSIONS: Using an algorithm for beam direction, shape and weight optimisation, large increases in the therapeutic ratio of liver plans could be obtained for reduced margins.

Adenoid cystic carcinoma of trachea treated with adjuvant hypofractionated tomotherapy. Case report and literature review.

Adenoid cystic carcinoma, also called cylindroma, is the second most common histological type of tracheal malignancy but represents 1% of all respiratory tract cancers. We report a case of a 59-year-old patient submitted to an incomplete resection of the trachea and subsequently treated with adjuvant tomotherapy. There have been no reports in the literature regarding intensity-modulated radiation therapy with linac or tomotherapy systems in adenoid cystic carcinoma of the trachea. The present clinical case demonstrates the feasibility of adjuvant intensity-modulated radiation therapy techniques for optimizing the dose coverage of the tumor bed while sparing surrounding normal tissues. A dosimetric comparison between the tomotherapy plan and a 3-dimensional conformal radiotherapy plan is also reported. We demonstrate that tomotherapy permits an increase in the dose per fraction without important acute adverse effects. At 24 months' follow-up, our patient shows no evidence of disease with negative histological findings.

Significant reduction of acute toxicity following pelvic irradiation with helical tomotherapy in patients with localized prostate cancer.

PURPOSE: To assess and quantify the possible benefit deriving from IMRT with Helical Tomotherapy (HTT) delivery to the pelvic nodal area in patients with prostate cancer in terms of reduction of acute and late toxicities. METHODS AND MATERIALS: Thirty-five patients candidate to radical or postoperative RT on whole pelvis (WPRT) were treated with HTT, while receiving a concomitant boost to the prostate or the prostatic bed (median 74.2 and 72 Gy, respectively) within a moderately hypofractionated (28-33 fractions; median HTT duration 44 days) regimen. Median and mean doses to whole pelvis were 52 and 54 Gy, respectively. One of the major goals of planning optimisation was to minimize the dose received by the intestinal cavity (IC) outside the nodal PTV. RESULTS: HTT resulted to be very efficient in sparing the IC even at dose levels below 30-35 Gy and guaranteed a significant sparing of bladder and rectum even at intermediate-low doses (V20-V40). No acute Grade 3 RTOG toxicity was recorded. Eighteen G1 and two G2 GU acute toxicities, 13 G1 upper GI acute toxicities, 8 G1 and 1 G2 acute proctitis were observed; no patient experienced G2 upper GI toxicity. After a median FU of 11.5 months (>10 in 18 patients) one case of late G3 GU toxicity was reported in one post-prostatectomy treated patient; no G2 late rectal bleeding or other GI toxicity was recorded. CONCLUSIONS: WPRT with HTT resulted in a very low incidence of acute Grade 2 and in the disappearance of acute Grade 3 toxicities.

Second Tumor Induction Risk in IMRT for Prostate Cancer: An Unbalanced Comparison Between Surgery and Radiotherapy?

The aim of this study was to evaluate the risk of second tumor induction for prostate patients treated with volumetric modulated arc therapy in age classes 50-70. Based on both age-dependent models and doses to critical organs, the risk of second tumor induction was evaluated simulating the small field (prostate and seminal vesicles) and large field (whole pelvis) for Helical Tomotherapy and Rapid Arc. The doses to the organs closest to the treatment volume were derived from treatment planning system data. Whereas, due to the lack of calculation algorithms where leakage and internal radiation scattering are unreliable at a large distance from target, the doses to the organs outside the treatment volume were measured in an anthropomorphic phantom. Doses from Image Guided Radiotherapy (IGRT) were also assessed on phantom measurements. The Lifetime Attributable Risk (LAR) for second tumor induction increases from 2.2 to 13.7% as irradiated volume increases and age decreases. IGRT could add a non-negligible factor to the risk when daily set-up verification with high-resolution modality is included. As prostate cancer is detected earlier, the probability of an increase in early stage patients rises, and life expectancy thus increases. Radiotherapy has improved its capability in the tailoring of the dose around the target at the cost of a greater dose to surrounding organs, thus increasing the risk of second tumor induction, especially for those patients expected to survive 15 y or more.