This is a retrospective, nationwide study of patients with newly diagnosed stage 4 cutaneous melanoma between 2010 and 2019, identified by national cancer database (NCDB). The goal of the study was to determine the rate of immune checkpoint inhibitor (ICI) usage in the wake of its FDA approval in addition to overall survival (OS). 16,831 patients with stage IV melanoma were identified; immunotherapy usage increased from 9% in 2010 to 39% in 2015, and 62% in 2019. OS increased from 7.7 months in 2010 to 17.5 months in 2018. In 2018, 38% of patients were still not receiving first-line ICI, use varied by patients’ socioeconomic factors.

(Open Access)

Reference (Pub-Med Link): Lamba, N., Ott, P. A., & Iorgulescu, J. B. (2022). Use of First-Line Immune Checkpoint Inhibitors and Association With Overall  Survival Among Patients With Metastatic Melanoma in the Anti-PD-1 Era. JAMA Network Open, 5(8), e2225459. https://doi.org/10.1001/jamanetworkopen.2022.25459

Key Institution: Harvard, Dana-Farber Cancer Institute, Brigham and Women’s Hospital
Keywords: Melanoma, Immunotherapy

A major concern in the treatment of Hodgkin lymphoma (HL), particularly when it comes to radiation, is the risk of late outcomes such as heart disease. Previous efforts to individually predict cancer treatment–related CVD have mostly focused on childhood cancer survivors and cannot be directly translated to survivors of adolescent and adult cancers because absolute and relative risks of treatment-related CVD differ by age. The aim of this study was to develop prediction models for coronary heart disease (CHD) and heart failure (HF) for survivors of adolescent/adult HL.

For model development, they included 1,400 5-year HL survivors treated between 1965 and 2000 and age 18-50 years at HL diagnosis, with complete data on administered chemotherapy regimens, radiotherapy volumes and doses, and cardiovascular follow-up. Using cause-specific hazard models, covariate-adjusted cumulative incidences for CHD and HF were estimated in the presence of competing risks of death. Age at HL diagnosis, sex, smoking status, radiotherapy, and anthracycline treatment were included as predictors. External validation for the CHD model was performed using a Canadian cohort of 708 HL survivors treated between 1988 and 2004 and age 18-50 years at HL diagnosis.

In this study, two separate prediction models were developed for CHD and HF, which were internally and externally validated with moderate to good discrimination and calibration. The models allow for an individual prediction of CHD or HF risk on the basis of treatment-related factors including sex, age at treatment, radiotherapy field or dose, anthracycline (dose), and smoking. Based on these models, 30-year risks ranged from 4% to 78% for CHD and 3% to 46% for HF, depending on risk factors.

These validated models define risk of coronary artery disease and congestive HF after treatment for Hodgkin lymphoma. Moving forward, these data can be used to identify HL survivors who might benefit from targeted screening for CVD and early treatment for CVD risk factors.

Reference (Pub-Med Link): de Vries, S., Haaksma, M. L., Jóźwiak, K., et al. (2022). Development and Validation of Risk Prediction Models for Coronary Heart Disease and Heart Failure After Treatment for Hodgkin Lymphoma. Journal of Clinical Oncology (online ahead of print). https://doi.org/10.1200/JCO.21.02613

Key Institution: Multi-Center
Keywords: Hodgkin Lymphoma

This article describes the data from a phase II trial in which prostate patients who have had prostatectomy with biochemical recurrence underwent SBRT for salvage treatment. Radiation dose was 30-34 Gy in 5 fractions delivered with either CT or MR guidance. A total of 100 patients were enrolled. Median follow-up was 29.5 months. Acute and late grade 2 GU toxicities were both 9%, while acute and late grade 2 GI toxicities were 5% and 0%. Three patients had grade 3 toxicity. Conclusion: post-prostatectomy SBRT was well tolerated at short-term follow-up.

(Open Access)

Reference (Pub-Med Link): Ma, T. M., Ballas, L. K., Wilhalme, H., et al. (2022). Quality-of-Life Outcomes and Toxicity Profile Among Patients With Localized Prostate Cancer After Radical Prostatectomy Treated With Stereotactic Body Radiation: The SCIMITAR Multicenter Phase 2 Trial. International Journal of Radiation Oncology, Biology, Physics. https://doi.org/10.1016/j.ijrobp.2022.08.041

Key Institution: UCLA

Keywords: Prostate

This report is a prospective phase II trial assessing the role of SBRT for patients with lung metastases from sarcoma. Sarcoma is a generally considered a radioresistant histology and patients with lung metastases are standardly managed with metastasectomy. This trial assessed the feasibility of treating up to 4 lung metastases ≤5cm in size using different fractionation schemes. Overall, there were 41 patients with 71 lung metastases and most patients were treated with 48 Gy/4 fx (86%). At 12 months, local control was 98.5% and local recurrence free survival was 58.8%.

Reference (Pub-Med Link): Navarria, P., Baldaccini, D., Clerici, E., et al. (2022). Stereotactic Body Radiation Therapy for Lung Metastases From Sarcoma in Oligometastatic Patients: A Phase 2 Study. International Journal of Radiation Oncology, Biology, Physics, 114(4), 762–770. https://doi.org/10.1016/j.ijrobp.2022.08.028

Key Institution: Humanitas Research Hospital, Milan, Italy

Keywords: Sarcoma, oligometastases

Muscle-invasive bladder cancer is the 6th most common cancer in men and 17th most common cancer in women worldwide. The current standard of care includes either radical cystectomy or trans urethral resection of bladder tumor followed by radiotherapy with or without radiosensitizing chemotherapy, also known as organ conserving therapy. No well-powered randomized trials compare these two approaches. BC2001 is the largest organ conservation trial in muscle-invasive bladder cancer, and compares chemoradiotherapy using 5-fluorouracil and mitomycin C vs RT alone. The primary analysis, published in 2012, reported significant improvement in locoregional control with chemoradiotherapy vs radiotherapy alone (HR 0.68 (0.48-0.96); p=0.03) with a median follow-up of five years. Now with 10-year median follow-up, improvement in locoregional control with chemoradiotherapy persists (HR 0.61 (0.43-0.86); p=0.004). As in the primary analysis, disease-related outcomes (disease-free survival, bladder cancer-specific survival, and overall survival) trended toward but did not reach statistical significance.

Given the absence of randomized data comparing radical cystectomy to organ conserving therapy, this further follow-up maintains the centrality of multimodal treatment to practitioners of bladder-conserving therapy but is unlikely to change practices in those who assert that radical cystectomy is the gold-standard for locally invasive bladder cancer despite patients’ continued reluctance to accept randomization to bladder-sparing or radical cystectomy-based approaches, likely making any randomized comparison out of reach. 

(Open Access)

Reference (Pub-Med Link): Hall, E., Hussain, S. A., Porta, N., et al. (2022). Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. European Urology, 82(3), 273–279. https://doi.org/10.1016/j.eururo.2022.04.017

Key Institution: The Institute of Cancer Research, London, UK
Keywords: Bladder

Mycosis fungoides is a chronic condition that warrants novel treatments that minimize long term side effects. Current standard of care includes radiotherapy or topical chemotherapy. This study looks at the efficacy and safety of topical hypericin ointment for early-stage mycosis fungoides in a large multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial. This study included 169 patients. Each cycle of topical hypericin is given twice a week followed by light treatment. They found a statistically significant clinical response with the hypericin ointment, including a 49% index lesion response rate (ILRR) after 3 cycles of hypericin. They did not find any serious adverse reactions. Further research is warranted to establish this treatment as a treatment option for early-stage mycosis fungoides.

(Open Access)

Reference (Pub-Med Link): Kim, E. J., Mangold, A. R., DeSimone, J. A. et al. (2022). Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial. JAMA Dermatology, 158(9), 1031–1039. https://doi.org/10.1001/jamadermatol.2022.2749

Key Institution: Perelman School of Medicine at University of Pennsylvania, Philadelphia
Keywords: FLASH, Lymphoma

A phase 2 study of neoadjuvant PD-1 immunotherapy using dostarlimab was conducted in 12 patients with stage II-III rectal adenocarcinoma patients with mismatch repair deficiency. Though the study protocol called for dostarlimab q3 weeks for 6 months followed by chemoRT and surgery, after 6 months of follow up upon completion of dostarlimab therapy, all 12 patients were found to have clinical complete response on MRI, FDG PET, DRE, biopsy, or endoscopy, and no patients at the time of this article’s publication (6-25 months of follow up) have received chemoRT or surgery. This could represent a truly groundbreaking paradigm shift in the management of colorectal cancer for patients with lynch syndrome, and warrants further follow up.

Reference (Pub-Med Link): Cercek, A., Lumish, M., Sinopoli, J., et al. (2022). PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. The New England Journal of Medicine, 386(25), 2363–2376. https://doi.org/10.1056/NEJMoa2201445

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

Anal cancer is more common in people with HIV than the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment and screening for cervical HSIL has led to a decrease in cervical cancer. However, little is known about the treatment of anal HSIL to prevent anal cancer. This article is the largest prospective phase 3 trial investigating how screening and treatment of HSIL can help prevent anal cell cancer development. Patients who were at least 35, HIV+, and had biopsy proven HSIL were either enrolled into active monitoring or an ablative procedure in 1:1 ratio. Of the 4459 patients who underwent randomization 4446 were analyzed with a median follow up of 25.8 months. In the treatment group, 9 cases of anal cancer were diagnosed. In the active monitoring group, 21 cases of anal cancer were diagnosed. The rate of progression to anal cancer was significantly lower in the treatment group than in the active monitoring group (Log-rank p-value: 0.03). Thus, for patients who are found to have biopsy proven anal HSIL, they should be treated with ablative therapy.

Reference (Pub-Med Link): Palefsky, J. M., Lee, J. Y., Jay, N., et al. (2022). Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. The New England Journal of Medicine, 386(24), 2273–2282. https://doi.org/10.1056/NEJMoa2201048

Key Institution: United States

Keywords: Anal Cancer

This is a retrospective review of 130 patients with node positive (N+) or common iliac node positive (M1a) prostate cancer treated with definitive radiotherapy. Patients were treated with long-term ADT and moderately or extremely hypofractionated RT to the prostate and pelvis, including the common iliac nodes. 75% of patients were staged with PSMA PET. At the time of biochemical failure, PSMA PET was acquired. At MFU 61 months, biochemical failure was similar (25.6% in the N+ group and 24.1% in the M1a group). Other outcomes were also similar between the 2 groups: distant metastasis (57% in N+ vs 73% in M1a, p=0.47), 5-year biochemical free survival (77.4% in N+ vs 70.4% in M1a, p=0.47), metastasis free survival (86.9% in N+ vs 79.4% in M1a, p=0.23), and overall survival (92.6% in N+ vs 90.1% in M1a, p=0.80). These findings suggest that common iliac node positive disease behaves similarly to other pelvic-node positive cases and should be treated (and perhaps staged) similarly.

Reference (Pub-Med Link): Chopade, P., Maitre, P., David, S., Panigrahi, G., Singh, P., Phurailatpam, R., & Murthy, V. (2022). Common Iliac Node-Positive Prostate Cancer Treated With Curative Radiation Therapy: N1 or M1a? International Journal of Radiation Oncology, Biology, Physics, 114(4), 711–717. https://doi.org/10.1016/j.ijrobp.2022.07.011

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

Managing localized prostate cancer in elderly men presents a challenge for clinicians. Current guidelines state that for patients with localized intermediate to high-risk prostate cancer, they should receive either prostatectomy or a combination of androgen deprivation therapy plus definitive radiotherapy, which may be external beam radiotherapy with or without brachytherapy boost. The purpose of this study was to analyze the oncological outcomes in elderly men after they received high-dose rate brachytherapy (HDB) boost.

They conducted an observational, retrospective, single-institution study in the country of France. 518 patients from the years 2008 to 2022 received a HDB boost and 380 were analyzed and split into two groups (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). With MFU of 72.6 months [67–83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85–92], 99% [97–100] and 94% [92–97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). There was no statistical difference between the two age-groups (Age <70 vs Age >70) in regards to late GI toxicity. The authors concluded that for intermediate and high-risk prostate cancer in the elderly, brachytherapy boost remains important to achieve optimal oncological outcomes. They felt that the toxicity profile of a brachytherapy boost appeared acceptable. Oftentimes, the elderly patients can be undertreated because their age is taken into account. They found that intermediate/high risk elderly prostate cancer patients benefits less from receiving standards of care. Brachytherapy boost remains efficient and feasible in the elderly.

(Open Access)

Reference (Pub-Med Link): Marotte, D., Gal, J., Schiappa, R., Gautier, M., Boulahssass, R., Chand-Fouche, M.-E., & Hannoun-Levi, J.-M. (2022). High-dose-rate brachytherapy boost for elderly patients with intermediate to high-risk prostate cancer: 5-year clinical outcome of the PROSTAGE cohort. Clinical and Translational Radiation Oncology, 35, 104–109. https://doi.org/10.1016/j.ctro.2022.05.001

Key Institution: Antoine Lacassagne Cancer Center
Keywords: Prostate cancer, Brachytherapy

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 

Patients (N=246) with resectable/borderline resectable pancreatic cancer were randomly assigned to receive preop chemoRT or immediate surgery in this phase 3 trial. Overall survival trended towards improvement with preop chemoRT (16.0 months, HR 0.78 (95% confidence interval [CI], 0.58 to 1.05), N=119) vs 14.3 months, (N=127), with P=0.096). R0 resection occurred in 71% vs 40% of patients with vs without preop chemoRT. Disease-free and locoregional failure-free survival were improved with vs without preop chemoRT. Overall survival was improved in a subset of patients who underwent resection and adjuvant chemotherapy with vs without preop chemoRT.

Reference (PubMed Link): Versteijne E, Suker M, Groothuis K, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Results of the dutch randomized phase iii preopanc trial. J Clin Oncol 2020;38:1763-1773.

Key Institution: Multi-Institutional (Netherlands)
Keywords: Pancreas, Surgery, Chemoradiation 

Twenty-one participants had locally advanced, unresectable, stage III NSCLC, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate hematologic, renal, and hepatic function.

Pembrolizumab was combined with concurrent chemoradiotherapy (weekly carboplatin and paclitaxel with 60 Gy of radiation in 2 Gy per d). Progression-free survival was good, with relatively few serious immune-related adverse events.

Consolidative immunotherapy following chemoradiation for locally advanced NSCLC was shown to improve survival in the PACIFIC trial. The use of concurrent immunotherapy with radiation in intriguing but there is little data regarding safety and efficacy. This Phase 1 study demonstrates that concurrent chemoimmunoradiotherapy is tolerable in this population, with further studies required to evaluate efficacy.

(Open Access)

Reference (PubMed Link): Jabbour SK, Berman AT, Decker RH, et al. Phase 1 trial of pembrolizumab administered concurrently with chemoradiotherapy for locally advanced non-small cell lung cancer: A nonrandomized controlled trial. JAMA Oncol 2020;6:1-8.

Key Institution: Multi-Institutional (Royal Marsden Hospital, Institute of Cancer Research, London, UK)
Keywords: Immunotherapy, Chemoradiotherapy, Locally Advanced Non-small Cell Lung Cancer 

This is a large, multi-institutional, retrospective, nonrandomized comparative effectiveness study that included 1483 adult patients with nonmetastatic, locally advanced cancer that was treated with concurrent chemotherapy and radiotherapy with curative intent. The primary endpoint was 90-day CTCAE adverse events of grade3 or above. The results showed that proton chemoradiotherapy was associated with a significantly lower relative risk of 90-day adverse event of at least grade 3 (relative risk = 0.31, with 95% confidence interval 0.65- 0.93, p=0.006), as well as decline in performance status during treatment (relative risk = 0.561, 95% confidence interval0.37 - 0.71, p<0.001). There was no difference in disease-free or overall survival.

Reference (PubMed Link): Baumann BC, Mitra N, Harton JG, et al. Comparative effectiveness of proton vs photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer. JAMA Oncol 2019.

Key Institution: Multi-Institutional (US)
Keywords: Proton therapy, toxicity

Cancer outcomes are relatively good for patients with hereditary retinoblastoma. However, long term survivors are at risk for developing secondary cancers as a result of radiotherapy. This study analyzed 952 long-term survivors diagnosed between 1914 and 2006. The authors found that there were 105 bone and 124 soft tissue sarcomas, more than half in the head and neck (in/near the radiation field), one quarter in the body and extremities, and about 1/5th elsewhere. These were diagnosed as early as early childhood and well into adulthood. These data provide some guidance as to the risk of developing secondary sarcomas after radiation therapy in childhood and point to the need for effective and risk-based screening. 

(Open Access)

Reference (PubMed Link): Kleinerman RA, Schonfeld SJ, Sigel BS, et al. Bone and soft-tissue sarcoma risk in long-term survivors of hereditary retinoblastoma treated with radiation. J Clin Oncol 2019;37:3436-3445.

Key Institution: National Cancer Institute, Bethesda, MD
Keywords: Retinoblastoma, radiation, secondary malignancy 

471 patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), of whom 251 were early stage, 76 were intermediate stage, and 144 were advanced stage.  All received first line treatment in the randomized GHSG HD7 to HD15 studies, which consisted of radiation alone, chemotherapy alone, or chemo-RT. 

Median follow up was 9.2 years. PFS and OS estimates were 75.5% and 92.1% respectively.  Early stage PFS and OS were 79.7% and 93.3%, intermediate stage PFS and OS were 72.1% and 96.2%, and advanced stage PFS and OS were 69.8% and 87.4%.  Patients older than 45 years and with splenic involvement at diagnosis had worse survival outcomes, as did patients with liver or bone marrow involvement. 10% of patients developed a secondary malignancy, of which almost half were solid tumors.  Only 9% of patients died. Among these, the majority of causes of death were from secondary malignancies or from non-malignant conditions possibly associated with RT or chemotherapy (such as cardiovascular disease), rather than from NLPHL. 

Given the good cause-specific survival of patients with NLPHL treated on GHSG protocols, treatment optimization with consideration of long-term side effects from radiation and/or chemotherapy should be evaluated. 

Reference (PubMed Link): Eichenauer DA, Plutschow A, Fuchs M, et al. Long-term follow-up of patients with nodular lymphocyte-predominant hodgkin lymphoma treated in the hd7 to hd15 trials: A report from the german hodgkin study group. J Clin Oncol 2019:Jco1900986.

Key Institution: German Hodgkin Study Group
Keywords: Hodgkin Lymphoma, RT, chemotherapy, chemoradiotherapy, secondary malignancy