This is a prospective randomized Phase II study of 126 patients with borderline resectable pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX with or without neoadjuvant SBRT / hypofractionated RT prior to surgery. Patients were treated with 8 cycles of mFOLFIRINOX or 7 cycles of mFOLFIRINOX followed by SBRT (33-40 Gy in 5 Fx) or hypofractionated RT (25 Gy in 5 Fx). Patients without disease progression underwent pancreatectomy followed by 4 cycles of postoperative FOLFOX6. The primary endpoint was 18-month OS compared with historical control rate of 50%. The SBRT arm was closed early due to low rates of R0 resection (33% vs 57% in the FOLFIRINOX arm). The 18-month OS was 66.7% vs 47.3% in favor of the neoadjuvant FOLFIRINOX alone arm, although lack of full accrual in the SBRT arm resulted in an inability to conclude statistical efficacy. This study demonstrates that in this patient population, there is no apparent benefit to the addition of SBRT to FOLFIRINOX for borderline resectable patients. The authors do not speculate on the possible reasons for lower rates of R0 resection in the SBRT arm. It is unclear from the manuscript what level of experience the participating centers have in performing pancreatectomies in a radiated field.

Reference (Pub-Med Link): Katz, M. H. G., Shi, Q., Meyers, J. et al. (2022). Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial. JAMA Oncology, 8(9), 1263–1270. https://doi.org/10.1001/jamaoncol.2022.2319

Key Institution: Multi-institutional, USA
Keywords: Pancreatic Cancer, SBRT

In this prospective pilot in silico trial investigators at Washington University treated 8 patients with abdominal oligometastases using SBRT to a dose of 50 Gy in 5 fractions. Patients were re-planned based on daily CT scans collected on the Ethos platform using the Varian Ethos emulator. Stomach and bowel dose was exceeded in 30/40 fractions delivered using the original plans Only 2/40 OAR violations were present in the adapted plans. Target coverage were also improved by adaptation. Adaptation required a median of 23 minutes (range 11-47 minutes).

Reference (Pub-Med Link): Schiff, J. P., Stowe, H. B., Price, A. et al. (2022). In Silico Trial of Computed Tomography-Guided Stereotactic Adaptive Radiation Therapy (CT-STAR) for the Treatment of Abdominal Oligometastases. International Journal of Radiation Oncology, Biology, Physics. https://doi.org/10.1016/j.ijrobp.2022.06.078

Although several prominent randomized clinical trials have revolutionized the use of local therapy in so-called oligometastatic patients, data regarding long-term outcomes remain to be defined. Additionally, the refinement of these clinical strategies specific to each histology may ultimately be necessary given that the underlying disease biology may affect clinical responses to oligometastasis-directed therapy.

In that context, the current clinical trial sought to evaluate hormone therapy and local metastasis-directed therapy to oligometastatic prostate cancer. This prospective study treated 29 patients with fractionated radiotherapy and ADT. About half the subjects had de novo oligometastatic disease and half had oligorecurrence. Over a 10-year median follow-up, PFS was approximately 2 years. However, ~60% of patients had durable local control of the treated lesions at last follow-up. De novo metastatic patients did better than oligorecurrent patients, suggesting different biology between the 2 disease states.

Overall, rather than being groundbreaking itself, this study fits as an orthogonal validation to larger studies showing the benefit of local therapy in oligometastatic patients.

Reference (Pub-Med Link): Hao, C., Ladbury, C., Lyou, Y., Manoukian, S., et al. (2022). Long-Term Outcomes of Patients on a Phase II Prospective Trial of Oligometastatic  Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation and External Beam Radiation. International Journal of Radiation Oncology, Biology, Physics, 114(4), 705–710. https://doi.org/10.1016/j.ijrobp.2022.06.085

Key Institution: City of Hope, Los Angeles, CA

Keywords: Oligometastases, Prostate

This is a prospective single-arm phase 2 study conducted at 8 US medical centers enrolling men 50 years of age and older with biopsy confirmed, unilateral, MRI-visible, intermediate risk, treatment naïve, primary prostate adenocarcinoma. Patients were treated with MRI-guided focused ultrasound. The co-primary endpoints were oncological outcomes (absence of GG2+ and higher cancer at 6- and 24-months after treatment) and safety (AEs up to 24 months after treatment). At 2 years, 88% of men had no evidence of GG2+ prostate cancer in the treated area. 60% had no evidence of GG2+ disease in the whole-gland on biopsy at 24 months. There were no G4/5 AEs reported. There was one grade 3 UTI reported. This study demonstrates that partial gland, focused US can be used to treat carefully selected men with intermediate risk prostate cancer with an acceptable side effect profile. However, the high rates of progression in the untreated areas of the prostate cast doubt on the utility of this approach. Nevertheless, this can be presented in the “T” area of a SWOT analysis for prostate cancer radiotherapy.

Reference (Pub-Med Link): Ehdaie, B., Tempany, C. M., Holland, F., et al.  (2022). MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study. The Lancet. Oncology, 23(7), 910–918. https://doi.org/10.1016/S1470-2045(22)00251-0

Key Institution: Multi-institutional, USA

Keywords: Prostate

This is a retrospective patterns of care study of 352 randomly selected patient records of patients with ALK+ NSCLC on 1st-line ALK inhibitor monotherapy. The primary outcome was brain-directed local treatment within 4 months. Of the 352 patients, 146 had brain metastases. 104/146 received CNS-directed local therapy, predominantly RT alone. SRS monotherapy was more common than WBRT monotherapy (53% vs 39%). Multivariable analysis demonstrated that patients who had their first brain metastasis during or after 2017 had a decreased rate of receiving brain directed therapy, adjusted incidence ratio of 0.63 (95% CI: 0.41 – 0.95, p=0.026). There was no change in the proportion receiving SRS vs WBRT. This study demonstrates a decreasing use of CNS directed therapy for patients with NSCLC brain metastasis on first line ALK inhibitors. This study provides evidence in support of general observations that the use of radiotherapy for brain metastases is declining with the advent of systemic agents with increasing intracranial activity. It remains to be seen, however, which patients are most appropriate for this approach.

(Open Access)

Reference (Pub-Med Link): Kumar, S., Wang, X., Pittell, H., Calip, G. S., Weiss, S. E., Meyer, J. E., & Royce, T. J. (2022). Real-world Use of Radiation for Newly Diagnosed Brain Metastases in Patients With ALK-positive Lung Cancer Receiving First-line ALK Inhibitor. International Journal of Radiation Oncology, Biology, Physics, 114(4), 627–634. https://doi.org/10.1016/j.ijrobp.2022.07.010

Key Institution: Multi-institutional, USA

Keywords: Brain, Metastasis

This trial was a randomized, multicenter, phase 3 trial that included patients with a persistently detectable or initially undetectable and rising PSA of between 0.1 and 2.0 after prostatectomy. Patients had pT2 or pT3 disease, Gleason score of 9 or less, and good performance status. These patients were randomized to prostate bed radiation therapy to 64.8 Gy-70.2 Gy at 1.8 Gy per fraction daily alone, or the same regimen plus short-term ADT or prostate bed radiation plus lymph node radiation to 45 Gy at 1.8 Gy per fraction and then a cone down to the PTV for 19.8-25.2 Gy plus ADT.

Authors looked at a primary end point of freedom from progression, defined as biochemical failure per the Phoenix definition, clinical failure, or death. 1716 were eligible for the final evaluation and at the interim analysis, the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (p<0.0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). The 5-year freedom from progression rates in all patients were 70.9%, 81.3%, and 87.4% in groups 1, 2, and 3 respectively. Adverse events were more common in group 3, but late toxicities were similar between the three groups.

The authors conclude that the addition of ADT to salvage prostate bed radiation improves outcomes, and the addition of pelvic lymph node irradiation further improves outcomes without any significant differences in late toxicities.

Reference (Pub-Med Link): Pollack, A., Karrison, T. G., Balogh, A. G., et al. (2022). The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet (London, England), 399(10338), 1886–1901. https://doi.org/10.1016/S0140-6736(21)01790-6

Key Institution: Multi-Center, International

Keywords: Prostate

This systematic review and meta-analysis of 7 studies evaluated overall survival following WBRT with or without SRS boost and SRS for SCLC brain metastases. Survival after SRS was not inferior to WBRT. Median OS after first-line SRS was estimated at 8.7 months. At 12 months, local and distant brain control rates were 78% and 58%, which are comparable with rates seen in other histologies. These findings also held true among patients who had not received prior PCI. In summary, among select patients, survival and intracranial disease control after SRS appear comparable to those treated with WBRT.

Reference (Pub-Med Link): Gaebe, K., Li, A. Y., Park, A., Parmar, A., et al. (2022). Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis. The Lancet. Oncology, 23(7), 931–939. https://doi.org/10.1016/S1470-2045(22)00271-6

Key Institution: University of Toronto

Keywords: Brain, metastasis

This is a retrospective review of 220 patients treated with definitive SBRT for non-metastatic prostate cancer treated to either the prostate alone (n = 118) or the prostate plus pelvic lymph nodes (n = 102). Dose to the prostate was 36.25 Gy in 5 Fx, with SIB to 25 Gy in 5 Fx for those receiving pelvic LN coverage. LN coverage was associated with increased G2 GI toxicity (29.4% vs 14.7%, p=0.008) and late G2 urinary toxicity (45.6% vs 25%, p=0.003). There was one case of G3 urinary obstruction in the prostate only group, and both groups had similar rates of late G3 toxicities (2.5% urinary toxicity, 1% GI). Though incidence of severe toxicity was low for Prostate SBRT with SIB to pelvic lymph nodes, there was a significant increase in acute GI and late GU toxicity. This retrospective study supports the notion that SIB coverage of pelvic lymph nodes is feasible, with an associated risk of increased low-grade toxicities.

Reference (Pub-Med Link): Murthy, V., Adsul, K., Maitre, P., et al. (2022). Acute and Late Adverse Effects of Prostate-Only or Pelvic Stereotactic Radiation Therapy in Prostate Cancer: A Comparative Study. International Journal of Radiation Oncology, Biology, Physics, 114(2), 275–282. https://doi.org/10.1016/j.ijrobp.2022.05.050

Key Institution: Tata Memorial Hospital, Mumbai, India
Keywords: Prostate

The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long term disease control if all sites of disease can be ablated. Although there have been several retrospective studies, there is limited randomized data. This article reports the long-term update of the SABR COMET trial which randomized patients with oligometastatic disease, defined as a controlled primary malignancy with 1-5 metastatic lesions, to palliative standard of care vs standard of care plus the addition of SABR. Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n 5 18), lung (n 5 18), colorectal (n 5 18), and prostate (n 5 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P5.006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P 5 .001). There were no new grade 2-5 adverse events and no differences in QOL between arms. At a median follow up of 51 months, there was a large statistically significant difference in overall survival, 5-yr OS (17.7% vs 42.3%) with the addition of SABR. There were no new safety concerns and there was no significant detriment on QOL. These promising results, pending confirmation in phase III randomized studies, support the expanded use of SABR/SBRT for patients with oligometastatic disease.

(Open Access)

Reference (PubMed Link): Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: Long-term results of the sabr-comet phase ii randomized trial. J Clin Oncol 2020:Jco2000818.

Key Institution: Multi-Institutional
Keywords: Oligometastases, SBRT, COMET trial

Several dosimetric studies and retrospective studies have suggested that proton beam therapy could reduce normal tissue toxicity compared with IMRT. However, proton beam therapy is substantially more expensive, and there is insufficient evidence that proton beam therapy leads to clinically meaningful differences in patient outcomes. In this single-institution randomized trial, the authors compared proton beam therapy and IMRT for locally advanced esophageal cancer. The authors found that proton beam therapy significantly reduced the total toxicity burden (TTB) and rate of post-operative complications compared with IMRT with similar rates of PFS and OS at 3 years. Remarkably, the postoperative complication score was 7.6 times higher for patients treated with IMRT. Interestingly, there were no significant differences in quality of life between the arms. This study provides the first randomized evidence that proton beam therapy can improve patient outcomes over IMRT. However, the primary endpoint of TTB has not been previously validated, and it is unclear that an improvement in TTB can economically justify routine use of proton beam therapy for esophageal cancer. The currently ongoing NRG-GI006 trial will help to evaluate the findings of this trial in a larger multi-institutional setting.

Reference (PubMed Link): Lin SH, Hobbs BP, Verma V, et al. Randomized phase iib trial of proton beam therapy versus intensity-modulated radiation therapy for locally advanced esophageal cancer. J Clin Oncol 2020;38:1569-1579.

Key Institution: Multi-Institutional
Keywords: Locally advanced esophageal cancer, proton beam therapy, total toxicity burden, NCT01512589