Prostate cancer-specific positron emission tomography (pcPET) has been shown to detect sites of disease recurrence at serum prostate-specific antigen (PSA) levels that are lower than those levels detected by conventional imaging. Commonly used pcPET radiotracers in the setting of biochemical recurrence are reviewed including carbon 11/fludeoxyglucose 18 (F-18) choline, gallium 68/F-18 prostate-specific membrane antigen (PSMA), and F-18 fluciclovine. Review of the literature generally favors PSMA-based agents for the detection of recurrence as a function of low PSA levels. Positive gallium 68/F-18 PSMA positron emission tomography/computed tomography scans detected potential sites of recurrence in a median 51.5% of patients when PSA level is <1.0 ng/mL, 74% of patients when PSA level is 1.0 to 2.0 ng/mL, and 90.5% of patients when PSA level is >2.0 ng/mL. Review of carbon 11/fludeoxyglucose 18 (F-18) choline and F-18 fluciclovine data commonly demonstrated lower detection rates for each respective PSA cohort, although with some important caveats, despite having similar operational characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new insight into the early patterns of disease spread, which has prompted judicious reconsideration of additional local therapy after either prostatectomy, definitive radiation therapy, or postprostatectomy radiation therapy. This review discusses the literature, clinical utility, availability, and fundamental understanding of pcPET imaging needed to improve clinical practice.

The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision-making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Because scarce clinical data exist to inform decisions at this time, the American Society for Radiation Oncology convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. During the American Society for Radiation Oncology workshop, several main points emerged, which are discussed in this manuscript: (1) variants of uncertain significance should be considered nondeleterious until functional genomic data emerge to demonstrate otherwise; (2) possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; (3) deleterious ataxiatelangiesctasia gene mutations may modestly increase second cancer risk after radiation therapy, and thus follow-up for these patients after indicated radiation therapy should include second cancer screening; (4) conveying to patients the difference between relative and absolute risk is critical to decision-making; and (5) more work is needed to assess the impact of tumor somatic alterations on the probability of response to radiation therapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

The c-Met/hepatocyte growth factor (HGF) receptor and its family members are known to promote cancer cell migration and invasion. Signaling within and beyond this pathway contributes to the systemic spread of metastases through induction of the epithelial-mesenchymal transition (EMT), a process also implicated in mediating resistance to current anticancer therapies, including radiation. Induction of c-Met has also been observed upon irradiation, suggesting that c-Met participates in radiation-induced progression through the EMT. Hence c-Met inhibition is an attractive target for potentially mitigating radiation resistance. This article summarizes key findings regarding cross-talk between radiation therapy and c-Met and discusses studies done to date in which c-Met inhibition was used as a strategy to increase cellular radiosensitivity.

Background and Purpose Improved radiation delivery and planning has allowed, in some instances, for the retreatment of thoracic tumors. We investigated the dose limits of the aorta wherein grade 5 aortic toxicity was observed after reirradiation of lung tumors. Material and Methods In a retrospective analysis, 35 patients were identified, between 1993 and 2008, who received two rounds of external beam irradiation that included the aorta in the radiation fields of both the initial and retreatment plans. We determined the maximum cumulative dose to 1 cm3 of the aorta (the composite dose) for each patient, normalized these doses to 1.8 Gy/fraction, and corrected them for long-term tissue recovery between treatments (NIDR). Results The median time interval between treatments was 30 months (range, 1–185 months). The median follow-up of patients alive at analysis was 42 months (range, 14–70 months). Two of the 35 patients (6%) were identified as having grade 5 aortic toxicities. There was a 25% rate of grade 5 aortic toxicity for patients receiving composite doses ≥120.0 Gy (vs. 0% for patients receiving <120.0 Gy) (P=0.047). Conclusions Grade 5 aortic toxicities were observed with composite doses ≥120.0 Gy (NIDR ≥90.0 Gy) to 1 cm3 of the aorta.

Background Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. Objective To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. Design, setting, and participants Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. Intervention C-11 choline positron emission tomography/computed tomography (CholPET). Outcome measurements and statistical analysis Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. Results and limitations Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p < 0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p = 0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. Conclusions CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. Patient summary We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

Purpose To evaluate C-11 choline PET/CT (CholPET) in staging and determining patterns of recurrence in prostate cancer patients with rising PSA post prostatectomy radiotherapy (RT). Materials and Methods The study includes patients with biochemical failure following post-prostatectomy RT who underwent CholPET between 2008 and 2015. Patient and disease characteristics were examined in relation to sites of recurrence. All RT dosimetry records were reviewed, and recurrences were mapped on a representative CT dataset with their relationship relative to the irradiated fossa field as out-of-field (OOF), edge-of-field (EOF; recurrence within <45Gy isodose lines), or in-field (IF; recurrence within ≥45 Gy isodose lines). Results Forty-one patients were identified with 121 sites of recurrence (median 2 sites; IQR 1-4). The median PSA at CholPET was 3.1 (IQR 1.9-5.6) ng/mL. Median interval from RT to biochemical failure was 24 (IQR: 10-46) months, with recurrence identified on CholPET at a median of 15 (IQR 7-28) months from biochemical failure. Histologic confirmation of recurrence was obtained in 20 (49%) patients; with the remainder confirmed by treatment response. Five patients (12%) had IF recurrences, 10 patients (24%) had EOF recurrences (median dose 10 Gy; IQR 5-30 Gy), and 36 patients (88%) had OOF recurrences. Ten patients had combination failures: 6 (15%) EOF/OOF and 4 (10%) IF/OOF. Fifty-seven (47%) of recurrences were pelvic nodal sites inferior to the L5-S1 interspace of which 52 (43%) are within a pelvic RT field. Eighty-one (67%) of recurrences were nodal and inferior to the aortic bifurcation. Conclusions Using CholPET, we found that the majority of patients evaluated for biochemical failure recurred outside of the post-prostatectomy RT field. Furthermore, most recurrence sites were nodal and inferior to the aortic bifurcation. These results provide data which may be useful for examining strategies that include elective lymph node irradiation in post-prostatectomy patients.

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