Citations

The purpose of the present study was to compare the impact of pulmonary function, body habitus, and stereotactic body radiation therapy (SBRT) immobilization on setup and reproducibility for upper lung tumor. From 2008 through 2011, our institution's prospective SBRT database was searched for patients with upper lung tumors. Two SBRT immobilization strategies were used: full‐length BodyFIX and thermoplastic S‐frame. At simulation, free‐breathing, four‐dimensional computed tomography was performed. For each treatment, patients were set up to isocenter with in‐room lasers and skin tattoos. Shifts from initial and subsequent couch positions with cone‐beam computed tomography (CBCT) were analyzed. Accounting for setup uncertainties, institutional tolerance of CBCT‐based shifts for treatment was 2, 2, and 4 mm in left–right, anterior–posterior, and cranial–caudal directions, respectively; shifts exceeding these limits required reimaging. Each patient's pretreatment pulmonary function test was recorded. A multistep, multivariate linear regression model was performed to elucidate intervariable dependency for three‐dimensional calculated couch shift parameters. BodyFIX was applied to 76 tumors and S‐frame to 17 tumors. Of these tumors, 41 were non–small cell lung cancer and 15 were metastatic from other sites. Lesions measured , 1.1 to 2 (50%), 2.1 to 3 (25%), and cm. Errors from first shifts of first fractions were significantly less with S‐frame than BodyFIX (). No difference in local control (LC) was found between S‐frame and BodyFIX (); two‐year LC rate was 94%. Multivariate modeling confirmed that the ratio of forced expiratory volume in the first second of expiration to forced vital capacity, body habitus, and the immobilization device significantly impacted couch shift errors. For upper lung tumors, initial setup was more consistent with S‐frame than BodyFIX, resulting in fewer CBCT scans. Patients with obese habitus and poor lung function had more SBRT setup uncertainty; however, outcome and probability for LC remained excellent.PACS number: 89.20.‐a

255 Background: The purpose of this study was to identify site-specific recurrence patterns for patients (pts) with biochemical recurrence (BCR) after prostatectomy (RP) using C-11 Choline PET/CT (C11Ch) and 3T pelvic MRI with endorectal coil (pMRI). Methods: Between 2008 and 2006, 2,466 men underwent C11Ch and pMRI for BCR after RP. From this cohort, we identified 261 pts who received no adjuvant or salvage therapy (androgen deprivation or radiation). Suspected radiographic relapse was confirmed by biopsy (46%) or progression/response to treatment in concordance with subsequent rise/decline in PSA (54%). Results: Of the 261 men evaluated, 202 (75%) had positive pMRI, C11Ch or both. Seventy nine (39%), 105 (52%) and 18 (9%) pts had high, intermediate, and low risk CaP, respectively at RP. Median PSA at the time of positive scan was 2.3 ng/mL, with a median time from BCR to radiographic disease identification of 15 months. Of these 202 men, 67 (33%) harbored prostate fossa recurrence only, 44 (22%) had a combination of local and metastatic disease and 91 (45%) had metastatic disease without local recurrence. Forty (20%) pts had pelvic nodal recurrence only and 18 (9%) had perirectal nodal involvement. Median PSA for pts with local only recurrence, distant metastases only, and local + distant disease was 2.3, 2.7 and 2.2 ng/mL, respectively, with a median interval from BCR to positive scan of 16.7, 7.9 and 11 months. Imaging revealed that 33% to 66% of our cohort would have all sites of disease treated by salvage RT depending on the extent of the treatment field Conclusions: C11Ch and pMRI were used to identify recurrence patterns in pts with BCR after RP only. At median PSA of 2.3 ng/ml, our study demonstrates a low rate of local-only recurrence, higher than anticipated frequency of metastatic recurrence with peak frequency within the pelvic lymph nodes, and substantial perirectal recurrences. Despite the high rates of distant recurrences, 2/3 of our cohort had their disease limited to the pelvis and could be potential candidates for local therapies, including salvage radiation.

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1 + CD11a hi CD8 + ) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8 + T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility.

Abstract We investigated the influence of PD-1 expression on the systemic antitumor response (abscopal effect) induced by stereotactic ablative radiotherapy (SABR) in preclinical melanoma and renal cell carcinoma models. We compared the SABR-induced antitumor response in PD-1–expressing wild-type (WT) and PD-1–deficient knockout (KO) mice and found that PD-1 expression compromises the survival of tumor-bearing mice treated with SABR. None of the PD-1 WT mice survived beyond 25 days, whereas 20% of the PD-1 KO mice survived beyond 40 days. Similarly, PD-1–blocking antibody in WT mice was able to recapitulate SABR-induced antitumor responses observed in PD-1 KO mice and led to increased survival. The combination of SABR plus PD-1 blockade induced near complete regression of the irradiated primary tumor (synergistic effect), as opposed to SABR alone or SABR plus control antibody. The combination of SABR plus PD-1 blockade therapy elicited a 66% reduction in size of nonirradiated, secondary tumors outside the SABR radiation field (abscopal effect). The observed abscopal effect was tumor specific and was not dependent on tumor histology or host genetic background. The CD11ahigh CD8+ T-cell phenotype identifies a tumor-reactive population, which was associated in frequency and function with a SABR-induced antitumor immune response in PD-1 KO mice. We conclude that SABR induces an abscopal tumor-specific immune response in both the irradiated and nonirradiated tumors, which is potentiated by PD-1 blockade. The combination of SABR and PD-1 blockade has the potential to translate into a potent immunotherapy strategy in the management of patients with metastatic cancer. Cancer Immunol Res; 3(6); 610–9. ©2015 AACR.