A phase I radiation dose-escalation study to determine the maximal dose of radiotherapy in combination with weekly gemcitabine in patients with locally advanced pancreatic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The primary objective of this study was to determine the maximum tolerated dose (MTD) of escalating doses of radiotherapy (RT) concomitantly with a fixed dose of gemcitabine (300 mg/m²/week) within the same overall treatment time.</p> <p>Methods</p> <p>Thirteen patients were included. Gemcitabine 300 mg/m²/week was administered prior to RT. The initial dose of RT was 45 Gy in 1.8 Gy fractions, escalated by adding 5 fractions of 1.8 Gy (one/week) to a dose of 54 Gy with a total duration kept at 5 weeks. All patients received a dynamic MRI to assess the pancreatic respiratory related movements. Toxicity was scored using the RTOG-EORTC toxicity criteria.</p> <p>Results</p> <p>Three of six patients experienced an acute dose limiting toxicity (DLT) at the 54 Gy dose level. For these patients a grade III gastro-intestinal toxicity (GI) was noted. Patients treated at the 45 Gy dose level tolerated therapy without DLT. The 54 Gy dose level was designated as the MTD and was deemed not suitable for further investigation.</p> <p>Between both dose levels, there was a significant difference in percentage weight loss (p = 0.006) and also in cumulative GI toxicity (p = 0.027). There was no grade 3 toxicity in the 45 Gy cohort versus 4 grade 3 toxicity events in the 54 Gy cohort. The mean dose to the duodenum was significantly higher in the 54 Gy cohort (38.45 Gy vs. 51.82 Gy; p = 0.001).</p> <p>Conclusion</p> <p>Accelerated dose escalation to a total dose of 54 Gy with 300 mg/m²/week gemcitabine was not feasible. GI toxicity was the DLT. Retrospectively, the dose escalation of 9 Gy by accelerated radiotherapy might have been to large. A dose of 45 Gy is recommended. Considering the good patient outcomes, there might be a role for the investigation of a fixed dose of gemcitabine and concurrent RT with small fractions (1.8 Gy/day) in borderline resectable or unresectable non-metastatic locally advanced pancreatic cancer.</p

IMRT-based optimization approaches for volumetric modulated single arc radiotherapy planning

This paper reports on an evaluation of 5 RapidArc(R) optimization approaches vs IMRT. This study includes 11 patients with adenocarcinoma of the prostate. Rectal Normal Tissue Complication Probability is used as a constraint in a dose escalation. RapidArc(R) rectal NTCP's are lower than those of IMRT (p=0.007). This allows a mean dose escalation of 2.1Gy([0.7Gy,3.5Gy]).status: publishe

Intrafractional prostate motion during online image guided intensity-modulated radiotherapy for prostate cancer

INTRODUCTION: Intrafractional motion consists of two components: (1) the movement between the on-line repositioning procedure and the treatment start and (2) the movement during the treatment delivery. The goal of this study is to estimate this intrafractional movement of the prostate during prostate cancer radiotherapy. MATERIAL AND METHODS: Twenty-seven patients with prostate cancer and implanted fiducials underwent a marker match procedure before a five-field IMRT treatment. For all fields, in-treatment images were obtained and then processed to enable automatic marker detection. Combining the subsequent projection images, five positions of each marker were determined using the shortest path approach. The residual set-up error (RSE) after kV-MV based prostate localization, the prostate position as a function of time during a radiotherapy session and the required margins to account for intrafractional motion were determined. RESULTS: The mean RSE and standard deviation in the antero-posterior, cranio-caudal and left-right direction were 2.3±1.5 mm, 0.2±1.1 mm and -0.1±1.1 mm, respectively. Almost all motions occurred in the posterior direction before the first treatment beam as the percentage of excursions>5 mm was reduced significantly when the RSE was not accounted for. The required margins for intrafractional motion increased with prolongation of the treatment. Application of a repositioning protocol after every beam could decrease the 1cm margin from CTV to PTV by 2 mm. CONCLUSIONS: The RSE is the main contributor to intrafractional motion. This RSE after on-line prostate localization and patient repositioning in the posterior direction emphasizes the need to speed up the marker match procedure. Also, a prostate IMRT treatment should be administered as fast as possible, to ensure that the pre-treatment repositioning efforts are not erased by intrafractional prostate motion. This warrants an optimized workflow with the use of faster treatment techniques.Budiharto T., Slagmolen P., Haustermans K., Maes F., Junius S., Verstraete J., Oyen R., Hermans J., Van den Heuvel F., ''Intrafractional prostate motion during online image guided intensity-modulated radiotherapy for prostate cancer'', Radiotherapy and oncology, vol. 98, no. 2, pp. 181-186, 2011.status: publishe

A multi-institutional analysis comparing adjuvant and salvage radiation therapy for high-risk prostate cancer patients with undetectable PSA after prostatectomy.

In men with adverse pathology at the time of radical prostatectomy (RP), the most appropriate timing to administer radiotherapy (RT) remains a subject for debate. To determine whether salvage radiotherapy (SRT) upon early prostate-specific antigen (PSA) relapse is equivalent to immediate adjuvant radiotherapy (ART) post RP. MATERIAL AND METHODS: 130 patients receiving ART and 89 receiving SRT were identified. All had an undetectable PSA after RP. Homogeneous subgroups were built based on the status (±) of lymphatic invasion (LVI) and surgical margins (SM), to allow a comparison of ART and SRT. Biochemical disease-free survival (bDFS) was calculated from the date of surgery and from the end of RT. The multivariate analysis was performed using the Cox Proportional hazard model. RESULTS: In the SM-/LVI- and SM+/LVI- groups, SRT was a significant predictor of a decreased bDFS from the date of surgery, while in the SM+/LVI+ group, there was a trend towards significance. From the end of RT, SRT was also a significant predictor of a decreased bDFS in three patient groups: SM-/LVI-, SM+/LVI- and SM+/LVI+. Gleason score >7 showed to be another factor on multivariate analysis associated with decreased bDFS in the SM-/LVI- group, from the date of surgery and end of RT. Preoperative PSA was a significant predictor in the SM-/LVI- group from the date of RP only. CONCLUSIONS: Immediate ART post RP for patients with high risk features in the prostatectomy specimen significantly reduces bDFS after RP compared with early SRT upon PSA relapse

Prospective Evaluation of (11)C-Choline Positron Emission Tomography/Computed Tomography and Diffusion-Weighted Magnetic Resonance Imaging for the Nodal Staging of Prostate Cancer with a High Risk of Lymph Node Metastases

BACKGROUND: Contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for lymph node (LN) staging of prostate cancer (PCa) are largely inadequate. OBJECTIVE: Our aim was to assess prospectively the sensitivity, specificity, and positive and negative predictive values for the LN staging by (11)C-choline positron emission tomography (PET)-CT and MR diffusion-weighted imaging (DWI) of the pelvis before retropubic radical prostatectomy (RRP) with extended pelvic LN dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: From February 2008 to August 2009, 36 patients with histologically proven PCa and no pelvic LN involvement on contrast-enhanced CT with a risk ≥10% but ≤35% at LN metastasis according to the enrolled in this study. INTERVENTION: Patients preoperatively underwent (11)C-choline PET-CT and DWI. Subsequently all patients underwent a wide RRP and an extended PLND. MEASUREMENTS: Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for LN status of (11)C-choline PET-CT and DWI were calculated with the final histopathology of the LNs as comparator. RESULTS AND LIMITATIONS: Seventeen patients (47%) had a pN1 stage, and 38 positive LNs were identified. On a LN region-based analysis, sensitivity, specificity, PPV, NPV, and the number of correctly recognised cases at (11)C-choline PET-CT were 9.4%, 99.7%, 75.0%, 91.0%, and 7.9%, respectively, and at DWI these numbers were 18.8%, 97.6%, 46.2%, 91.7%, and 15.8%, respectively. Twelve LN regions containing macrometastases, of which 2 had capsular penetration, were not detected by (11)C-choline PET-CT; 11 LNs, of which 2 had capsular penetration, were not detected by DWI. This is a small study with 36 patients, but we intend to recruit more patients. CONCLUSIONS: From this prospective histopathology-based evaluation of (11)C-choline PET-CT and DWI for LN staging in high-risk PCa patients, it is concluded that these techniques cannot be recommended at present to detect occult LN metastases before initial treatment.status: publishe

Prospective evaluation of 11C-choline positron emission tomography/computed tomography and diffusion-weighted magnetic resonance imaging for the nodal staging of prostate cancer with a high risk of lymph node metastases

BACKGROUND: Contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for lymph node (LN) staging of prostate cancer (PCa) are largely inadequate. OBJECTIVE: Our aim was to assess prospectively the sensitivity, specificity, and positive and negative predictive values for the LN staging by (11)C-choline positron emission tomography (PET)-CT and MR diffusion-weighted imaging (DWI) of the pelvis before retropubic radical prostatectomy (RRP) with extended pelvic LN dissection (PLND). DESIGN, SETTING, AND PARTICIPANTS: From February 2008 to August 2009, 36 patients with histologically proven PCa and no pelvic LN involvement on contrast-enhanced CT with a risk >/= 10% but </= 35% at LN metastasis according to the Partin tables were enrolled in this study. INTERVENTION: Patients preoperatively underwent (11)C-choline PET-CT and DWI. Subsequently all patients underwent a wide RRP and an extended PLND. MEASUREMENTS: Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for LN status of (11)C-choline PET-CT and DWI were calculated with the final histopathology of the LNs as comparator. RESULTS AND LIMITATIONS: Seventeen patients (47%) had a pN1 stage, and 38 positive LNs were identified. On a LN region-based analysis, sensitivity, specificity, PPV, NPV, and the number of correctly recognised cases at (11)C-choline PET-CT were 9.4%, 99.7%, 75.0%, 91.0%, and 7.9%, respectively, and at DWI these numbers were 18.8%, 97.6%, 46.2%, 91.7%, and 15.8%, respectively. Twelve LN regions containing macrometastases, of which 2 had capsular penetration, were not detected by (11)C-choline PET-CT; 11 LNs, of which 2 had capsular penetration, were not detected by DWI. This is a small study with 36 patients, but we intend to recruit more patients. CONCLUSIONS: From this prospective histopathology-based evaluation of (11)C-choline PET-CT and DWI for LN staging in high-risk PCa patients, it is concluded that these techniques cannot be recommended at present to detect occult LN metastases before initial treatment

Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement

Accurate staging modalities to diagnose lymph node involvement in patients with prostate cancer (PCa) are lacking. We wanted to prospectively assess sensitivity, specificity, and positive predictive value (PPV) and negative predictive value of (11)C-choline positron emission tomography (PET)-computed tomography (CT) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for nodal staging in patients with PCa at high risk for lymph node involvement.publisher: Elsevier articletitle: Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement journaltitle: Urologic Oncology: Seminars and Original Investigations articlelink: http://dx.doi.org/10.1016/j.urolonc.2014.11.008 content_type: article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe