Long-Term Results of Moderate Hypofractionation to Prostate and Pelvic Nodes Plus Androgen Suppression in High-Risk Prostate Cancer.

PURPOSE: Moderate hypofractionated radiation therapy (HypoRT) is an attractive alternative to conventionally fractionated radiation therapy for prostate cancer. However, most studies using HypoRT only included the prostate as the target volume. We report long-term outcomes of patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and HypoRT to the prostate and nodal areas with a simultaneous integrated boost technique. METHODS AND MATERIALS: Patients with localized, high-risk prostate cancer entered a prospective phase I/II study with a HypoRT regimen of 60 Gy/20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated radiation therapy with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT. Toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events v3. Outcomes rates were calculated by the actuarial method of Kaplan-Meier from the date of last radiation treatment until date of event. RESULTS: We report on the first 105 patients treated between October 2010 and February 2014. Median follow-up was 74 months, with 97% of patients followed for more than 36 months. Median ADT duration was 18 months. The worst grade 2 or higher late gastrointestinal or genitourinary toxicity was seen in 7% and 9%, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rates of grade ≥2 gastrointestinal or genitourinary toxicity were 2% and 3%, respectively, with no residual grade ≥3 toxicity. The 5- and 7-year actuarial overall survival and relapse free survival were 91% and 85% and 87% and 81%, respectively. CONCLUSIONS: The longest follow-up report of moderate HypoRT (plus ADT) to the prostate and pelvic nodes shows that this approach is feasible, well tolerated, and effective. It is convenient for patients and the health system. A larger randomized trial using this approach is warranted.

Response to stereotactic ablative radiotherapy in a novel orthotopic model of non-small cell lung cancer.

Stereotactic ablative radiotherapy (SABR) is the main treatment for inoperable early-stage non-small cell lung cancer (NSCLC). Despite the widespread use of SABR, the biological determinants of response to SABR remain poorly investigated. We developed an orthotopic NSCLC animal model to study the response to clinically-relevant doses of SABR. Image-guided intra-thoracic injection of NSCLC cells was performed in the right lung of nude rats. A highly conformal dose of 34 Gy was delivered in a single fraction using clinical photon energies. Animals were sacrificed 10-60 days post treatment. Lung tumors were assessed for tumor differentiation, proliferation and invasiveness. An analysis of 770 cancer-related genes was performed on tumor-derived cell lines from treated animals at early and late time points after SABR. The majority of animals receiving SABR demonstrated complete response (67%), while 33% demonstrated local failure. 50% of animals with complete response failed distantly. Analysis of cancer-related genes revealed significant differences between tumors treated with SABR and untreated tumors. SABR significantly modulated expression of genes involved in adhesion, migration and angiogenesis. In particular, interleukin-8 (IL8) which plays a critical role in promoting tumor invasion was found to be secreted at high levels after SABR. In vitro invasion assays confirmed SABR-induced invasion and demonstrated induction of IL-8 secretion in multiple NSCLC cell lines. Our findings underscore the importance of developing targeted therapies that can circumvent the pro-invasive effects of SABR in NSCLC.

Acute and late toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated pelvic radiation therapy.

PURPOSE: To report acute and late toxicity rates in patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and moderate hypofractionated radiation therapy (HypoRT) to the prostate and nodal areas. METHODS AND MATERIALS: Patients with localized, high-risk prostate cancer were treated with a HypoRT regimen of 60 Gy in 20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated RT with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT and was given to all patients. Acute and late toxicity were prospectively assessed and graded according to the Common Terminology Criteria for Adverse Events, version 3. RESULTS: A total of 105 patients treated between September 2010 and November 2013 were reviewed. Median follow-up was 41 months, with 97% of patients followed for more than 26 months. Median ADT duration was 18 months. Acute grade 2 or higher gastrointestinal (GI) or genitourinary (GU) toxicity was seen in 18 (17%) and 19 (17%) patients, respectively, with only 1 and 3 patients experiencing either a GI or GU acute grade 3 toxicity. The worst grade 2 or higher late GI and GU toxicity were seen in 7 (7%) and 8 (8%) patients, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rate of grade 2 GI and GU toxicity was 5% and 3%, respectively, with no residual grade ≥3 toxicity. The 48-month actuarial progression free survival is 82%. CONCLUSIONS: ADT with moderate HypoRT delivered with IMRT and an integrated simultaneous boost to the prostate (60 Gy) and pelvic nodes (44 Gy) in 20 fractions is feasible and well tolerated. This approach shortens treatment duration and is convenient for patients and the health system, and its results support a randomized trial.

Pelvic lymph node displacement in high-risk prostate cancer patients treated with image guided intensity modulated radiation therapy with 2 independent target volumes.

PURPOSE: To evaluate the displacement of the pelvic lymph node (PLN) target when using cone beam computed tomography (CBCT) for localization of the prostate in patients treated with simultaneous integrated boost. METHODS AND MATERIALS: High-risk prostate cancer patients treated with image guided intensity modulated radiation therapy with simultaneous integrated boost receiving 60 Gy in 20 fractions to the prostate and proximal seminal vesicles (PTV60) and 44 Gy in the same 20 fractions to the PLN (PTV44) were studied. Two hundred weekly CBCTs of 50 patients were retrospectively reviewed to assess the displacement of the iliac vessels compared with the simulation computed tomography. For each CBCT, possible displacements were analyzed at 3 levels of PTV44: a superior, middle, and inferior slice, making a total of 600 slices reviewed. Geographical miss (GM) was defined when any part of the iliac vessels on the CBCT was outside of the PTV44 contour. RESULTS: GM was found in 7 of the 600 CBCT slices, all in different patients. All GMs were of ≤5 mm. Four GMs occurred on the middle slice and 3 on the superior slice. In 3 cases, the GM was related to shifts ≥7 mm applied to the prostate. CONCLUSIONS: Our review suggests that for high-risk prostate cancer, the chance of not appropriately covering the PLN target after adjusting the prostate is low. GM was uncommon and in the order of only a few millimeters when it occurred.

Stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma: the McGill University experience.

PURPOSE: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. METHODS AND MATERIALS: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. RESULTS: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. CONCLUSIONS: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.