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