Radiation Oncology
RCT: Five-Fraction SBRT Noninferior to Conventional Radiotherapy in Localized Prostate Cancer
20 Oct, 2024 | 15:46h | UTCBackground: Prostate cancer poses a significant global health challenge, with radiotherapy being a common curative treatment for localized disease. Hypofractionation, delivering higher doses per session over fewer treatments, has potential benefits in efficacy and convenience. While moderately hypofractionated radiotherapy is established, the efficacy of stereotactic body radiotherapy (SBRT) delivering radiation in just five fractions remains uncertain.
Objective: To assess whether five-fraction SBRT is noninferior to conventionally or moderately hypofractionated radiotherapy regarding freedom from biochemical or clinical failure in patients with low-to-intermediate-risk localized prostate cancer.
Methods: In this phase 3, international, open-label randomized controlled trial (PACE-B), 874 men with stage T1–T2 prostate cancer, Gleason score ≤3+4, and prostate-specific antigen (PSA) ≤20 ng/mL were randomized 1:1 to receive SBRT (36.25 Gy in 5 fractions over 1–2 weeks) or control radiotherapy (78 Gy in 39 fractions over 7.5 weeks or 62 Gy in 20 fractions over 4 weeks). Androgen-deprivation therapy was not permitted. The primary endpoint was freedom from biochemical or clinical failure.
Results: Between August 2012 and January 2018, 874 patients were randomized (433 to SBRT and 441 to control radiotherapy) at 38 centers. Median age was 69.8 years, median PSA was 8.0 ng/mL, and 91.6% had intermediate-risk disease. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% in the SBRT group and 94.6% in the control group (unadjusted HR 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority). Cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects at 5 years was higher with SBRT (26.9% vs. 18.3%; P<0.001), while gastrointestinal toxic effects were similar between groups (10.7% vs. 10.2%; P=0.94). Overall survival did not differ significantly (HR for death, 1.41; 95% CI, 0.90 to 2.20).
Conclusions: Five-fraction SBRT was noninferior to conventional or moderately hypofractionated radiotherapy in terms of biochemical or clinical failure in patients with low-to-intermediate-risk localized prostate cancer. SBRT may be an effective treatment option but is associated with a higher incidence of medium-term genitourinary toxic effects.
Implications for Practice: SBRT offers equivalent oncologic efficacy with the convenience of fewer treatment sessions, potentially reducing patient burden and healthcare resource utilization. Clinicians should consider SBRT for eligible patients but must inform them about the increased medium-term risk of genitourinary toxic effects.
Study Strengths and Limitations: Strengths include a large sample size, multicenter design, standardized radiotherapy protocols, and exclusion of hormonal therapy, minimizing confounding factors. Limitations involve the applicability of findings only to patients similar to those in the trial; some may now opt for active surveillance, and results may not extend to higher-risk populations.
Future Research: Further studies are needed to evaluate long-term outcomes of SBRT, its role in higher-risk patients, and strategies to mitigate genitourinary toxic effects.
RCT: Stereotactic Body Radiotherapy Reduced Incontinence and Sexual Dysfunction vs. Prostatectomy in Localized Prostate Cancer
18 Sep, 2024 | 10:51h | UTCBackground: Men with localized prostate cancer have several treatment options, including prostatectomy and radiotherapy. Patient-reported outcomes (PROs) are crucial in guiding treatment decisions due to potential impacts on quality of life. However, randomized data comparing stereotactic body radiotherapy (SBRT) with prostatectomy are lacking.
Objective: To compare patient-reported urinary, bowel, and sexual outcomes at 2 years following SBRT versus prostatectomy in men with low- to intermediate-risk localized prostate cancer.
Methods: In the phase 3 PACE-A randomized controlled trial conducted in the UK from 2012 to 2022, 123 men with National Comprehensive Cancer Network (NCCN) low- to intermediate-risk localized prostate cancer were randomized 1:1 to receive either SBRT (36.25 Gy in five fractions) or prostatectomy. Androgen deprivation therapy was not permitted. The co-primary outcomes were the number of absorbent urinary pads used daily and the Expanded Prostate Index Composite (EPIC-26) bowel domain score at 2 years. Secondary outcomes included clinician-reported toxicity and sexual function.
Results: Among 110 men who received treatment (median age 65.5 years; median PSA 7.9 ng/ml; 92% intermediate-risk), 50 underwent prostatectomy and 60 received SBRT. At 2 years, 50% of prostatectomy patients reported using one or more urinary pads daily compared to 6.5% of SBRT patients (p < 0.001; difference 43%, 95% CI 25%–62%). Bowel domain scores were better for prostatectomy (median 100) than for SBRT (median 87.5; p < 0.001; mean difference 8.9, 95% CI 4.2–13.7). Sexual function scores were worse for prostatectomy (median 18) compared to SBRT (median 62.5; p < 0.001). Clinician-reported genitourinary and gastrointestinal toxicities were low in both groups.
Conclusions: SBRT was associated with significantly less urinary incontinence and sexual dysfunction but slightly worse bowel function compared to prostatectomy at 2 years in men with localized prostate cancer.
Implications for Practice: These findings provide preliminary evidence to inform treatment decisions for men with low- to intermediate-risk localized prostate cancer. SBRT may offer advantages in reducing urinary incontinence and sexual dysfunction, which are significant considerations for patients. Clinicians should also discuss the potential for increased bowel symptoms with SBRT.
Study Strengths and Limitations: Strengths include the randomized design, use of contemporary treatment modalities, and comprehensive assessment of PROs. Limitations involve the small sample size due to slow recruitment, differential dropout rates, and incomplete PRO responses at the 2-year mark.
Future Research: Larger-scale randomized trials are needed to confirm these findings, assess long-term outcomes beyond 2 years, and evaluate the impact on disease control and quality of life.
RCT: Comparing Perioperative Chemotherapy Alone to Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy in Resectable Gastric Cancer
14 Sep, 2024 | 18:23h | UTCBackground:
In the management of resectable gastric cancer, perioperative chemotherapy—chemotherapy administered both before (neoadjuvant) and after (adjuvant) surgery—is the standard of care in many Western countries. This approach is based on trials like MAGIC and FLOT4-AIO, which demonstrated improved survival with perioperative chemotherapy compared to surgery alone.
Preoperative chemoradiotherapy (the combination of chemotherapy and radiotherapy before surgery) has shown benefits in other gastrointestinal cancers, such as esophageal cancer, by downstaging tumors and potentially improving surgical outcomes. However, its efficacy in gastric cancer, especially when added to perioperative chemotherapy, has not been well-established.
Objective:
To determine whether adding preoperative chemoradiotherapy to standard perioperative chemotherapy improves overall survival compared to perioperative chemotherapy alone in patients with resectable gastric and gastroesophageal junction adenocarcinoma.
Methods:
- Study Design: International, phase 3, randomized controlled trial (TOPGEAR).
- Participants: 574 patients with resectable adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II or III), clinical stage T3 or T4, and considered suitable for curative surgery.
- Interventions:
1. Perioperative Chemotherapy Group (Control Group):
- Definition of Perioperative Chemotherapy: Chemotherapy administered both before (preoperative/neoadjuvant) and after (postoperative/adjuvant) surgery.
- Chemotherapy Regimens:
- Before 2017: Patients received three cycles before surgery and three cycles after surgery of either:
- ECF: Epirubicin, Cisplatin, and continuous-infusion Fluorouracil.
- ECX: Epirubicin, Cisplatin, and Capecitabine (an oral prodrug of fluorouracil).
- After 2017 Amendment: Patients received four cycles before surgery and four cycles after surgery of:
- FLOT: Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel.
- Before 2017: Patients received three cycles before surgery and three cycles after surgery of either:
2. Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy Group (Experimental Group):
- Modifications to Chemotherapy:
- Received one less cycle of preoperative chemotherapy compared to the control group to accommodate the addition of radiotherapy.
- Postoperative chemotherapy was the same as in the control group.
- Preoperative Chemoradiotherapy:
- Chemoradiotherapy Definition: Concurrent administration of chemotherapy and radiotherapy before surgery.
- Radiotherapy Regimen:
- Total dose of 45 Gy, delivered in 25 fractions over 5 weeks (1.8 Gy per fraction, 5 days per week).
- Target Area: Entire stomach, any perigastric tumor extension, and regional lymph nodes.
- Concurrent Chemotherapy During Radiotherapy:
- Continuous infusion of Fluorouracil (200 mg/m² per day) 7 days a week during radiotherapy.
- Alternatively, Capecitabine (825 mg/m² twice daily on days 1–5 of each radiotherapy week) could be used.
- Surgical Procedure:
- Surgery was performed 4–6 weeks after completion of preoperative therapy.
- Recommended surgery included total gastrectomy, subtotal distal gastrectomy, or esophagogastrectomy with D2 lymphadenectomy (removal of additional lymph node stations beyond the immediate perigastric nodes).
Endpoints:
- Primary Endpoint: Overall survival (time from randomization to death from any cause).
- Secondary Endpoints: Progression-free survival, pathological complete response rate (no residual tumor in the resected specimen), treatment-related toxic effects, and quality of life.
Results:
- Pathological Findings:
- Pathological Complete Response Rate:
- Higher in the experimental group (preoperative chemoradiotherapy) at 17% compared to 8% in the control group.
- Tumor Downstaging:
- More patients in the experimental group had their tumors downstaged to a lower T category and had fewer involved lymph nodes.
- Pathological Complete Response Rate:
- Survival Outcomes:
- Overall Survival:
- Median Overall Survival:
- Experimental Group: 46 months.
- Control Group: 49 months.
- Hazard Ratio for Death: 1.05 (95% CI, 0.83–1.31), indicating no significant difference between the groups.
- Median Overall Survival:
- Progression-Free Survival:
- Median progression-free survival was similar between the groups (31 months vs. 32 months).
- Overall Survival:
- Treatment Adherence:
- Preoperative Therapy Completion:
- High completion rates in both groups for preoperative chemotherapy.
- Slightly lower in the experimental group due to the addition of radiotherapy.
- Postoperative Chemotherapy Completion:
- Lower completion rates overall, with fewer patients in the experimental group completing postoperative chemotherapy (48% vs. 59%).
- Preoperative Therapy Completion:
- Adverse Events:
- Similar rates of grade 3 or higher toxic effects in both groups.
- No significant differences in surgical complications or postoperative mortality.
Conclusion:
Adding preoperative chemoradiotherapy to standard perioperative chemotherapy did not improve overall survival or progression-free survival in patients with resectable gastric and gastroesophageal junction adenocarcinoma, despite achieving higher pathological complete response rates and increased tumor downstaging. These findings suggest that the routine addition of preoperative chemoradiotherapy to perioperative chemotherapy does not confer additional survival benefits and should not change the current standard of care.
Clinical Implications:
- Standard Treatment Remains Perioperative Chemotherapy:
- Perioperative chemotherapy alone continues to be the standard approach for resectable gastric cancer.
- Regimens like FLOT are preferred due to their demonstrated efficacy.
- Role of Radiotherapy:
- Routine use of preoperative radiotherapy in addition to chemotherapy is not supported by this trial’s findings.
- Radiotherapy may still have a role in specific clinical scenarios, but not as a standard addition to perioperative chemotherapy.
- Future Directions:
- Further research may focus on identifying subgroups of patients who might benefit from chemoradiotherapy.
- Biomarker-driven approaches and personalized treatment strategies could optimize outcomes.
Network Meta-Analysis: Preoperative Chemoradiotherapy and Chemotherapy Equally Improve Survival in Esophagogastric Adenocarcinoma – JAMA Netw Open
17 Aug, 2024 | 19:21h | UTCStudy Design and Population: This network meta-analysis included 17 randomized clinical trials (RCTs) with a total of 2,549 patients, predominantly male (86.5%), with a mean age of 61 years. The study compared the effects of preoperative chemoradiotherapy (CRT) versus preoperative and/or perioperative chemotherapy, and surgery alone on overall survival and disease-free survival in patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG).
Main Findings: Both preoperative CRT plus surgery (HR, 0.75) and preoperative/perioperative chemotherapy plus surgery (HR, 0.78) significantly improved overall survival compared to surgery alone. Disease-free survival was similarly prolonged with both treatments. No significant difference was observed between CRT and chemotherapy in overall survival, though CRT was associated with higher postoperative morbidity.
Implications for Practice: The findings suggest that both preoperative CRT and preoperative/perioperative chemotherapy are effective in extending survival in AEG patients, with no clear superiority of one approach over the other. Clinicians can consider either modality based on patient-specific factors, although the increased morbidity associated with CRT warrants careful consideration.
RCT: Radiation therapy alone superior to chemoradiation in low-grade localized endometrial cancer recurrences
1 May, 2024 | 21:41h | UTCThis randomized clinical trial assessed the effectiveness of radiation therapy alone versus concurrent chemoradiation in treating localized recurrences of endometrial cancer. Conducted from February 2008 to August 2020, the study involved 165 patients who were randomized to receive either radiation therapy alone or chemoradiation with weekly cisplatin. Findings indicate that radiation therapy alone resulted in longer progression-free survival (PFS) compared to chemoradiation, with a median PFS not reached for radiation alone versus 73 months for chemoradiation. Additionally, radiation therapy demonstrated lower rates of acute toxicity. The study concluded that for patients with low-grade and primarily vaginal recurrences, radiation therapy alone is the preferable treatment option, offering excellent outcomes without the added toxicity of chemotherapy.
Reference (link to abstract – $ for full-text):
The Lancet Commission: Global projections and recommendations for managing the increasing burden of prostate cancer
27 Apr, 2024 | 18:42h | UTCThe Lancet Commission’s report on prostate cancer highlights the expected doubling of annual cases from 1.4 million in 2020 to 2.9 million by 2040, driven by demographic changes and increased life expectancy. This comprehensive analysis divides the issue into epidemiology, diagnostics, management of localized and advanced disease, emphasizing disparities between high-income countries (HICs) and low- and middle-income countries (LMICs). Key findings indicate that late diagnoses are common, particularly in LMICs, leading to worse outcomes. The Commission advocates for significant changes in the diagnostic pathways and increased use of current technologies tailored to available resources to improve outcomes. Education and awareness programs are recommended to facilitate early detection and shift the treatment paradigm from palliative to curative, focusing on surgery and radiotherapy. Without decisive action, the global mortality from prostate cancer is set to rise, highlighting the need for urgent interventions across all countries, with a special focus on underserved populations.
Reference:
Phase 2 RCT | Adding stereotactic body radiotherapy to immune checkpoint inhibitors fails to improve outcomes in solid tumor patients
9 Aug, 2023 | 15:28h | UTCCheckpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors: The CHEERS Phase 2 Randomized Clinical Trial – JAMA Oncology (link to abstract – $ for full-text)
See also: Visual Abstract
Commentary: Addition of SBRT to Immunotherapy in Advanced Solid Tumors – The ASCO Post
RCT | Upfront radiosurgery reduces tumor volume vs. a wait-and-scan approach in small- to medium-sized vestibular schwannoma
7 Aug, 2023 | 14:40h | UTCUpfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial – JAMA (free for a limited period)
See also: Visual Abstract
Commentary on Twitter
Among patients with small or medium vestibular schwannoma, a treatment strategy consisting of upfront radiosurgery was more effective at reducing tumor volume at 4 years than was the initial wait-and-scan approach. https://t.co/Qv3YZVsq2Q pic.twitter.com/aNeu7MJfl0
— JAMA (@JAMA_current) August 2, 2023
RCT | Dysphagia-optimized intensity-modulated radiotherapy better preserves swallowing function in pharyngeal cancer patients
25 Jul, 2023 | 13:52h | UTCCommentaries:
Radiation approach improves swallowing in head, neck cancer – MDedge
Commentary on Twitter
NOW OF: The (DARS) phase 3 RCT investigates if dysphagia-optimised intensity-modulated radiotherapy (IMRT) reduces radiation dose to the dysphagia and aspiration related structures and improves swallowing function compared with standard IMRT.#hncsmhttps://t.co/CzpxsNxx1N pic.twitter.com/xNgfm43tHE
— The Lancet Oncology (@TheLancetOncol) July 7, 2023
Phase 2 Trial | The addition of immunotherapy to stereotactic ablative radiotherapy may enhance EFS in early-stage NSCLC
25 Jul, 2023 | 13:36h | UTCStereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial – The Lancet (link to abstract – $ for full-text)
Systematic Review | Post-mastectomy RT likely lowers recurrence and improves survival in early breast cancer with 1-3 positive nodes
25 Jul, 2023 | 13:34h | UTC
RCT | Brachytherapy alone sufficient for intermediate-risk prostate cancer, no FFP improvement with additional EBRT
7 Jul, 2023 | 16:06h | UTCEffect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial – Journal of Clinical Oncology (link to abstract – $ for full-text)
ESTRO-ACROP guideline | Recommendations on implementation of breath-hold techniques in radiotherapy
22 Jun, 2023 | 14:51h | UTC
RCT | Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer
15 Jun, 2023 | 15:04h | UTC
M-A | Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy
5 Jun, 2023 | 13:29h | UTCRole of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis – The Lancet Oncology (free for a limited period)
Commentary from the author on Twitter
Our latest meta-analysis on #chemoradiation in nasopharyngeal cancer out in @TheLancetOncol
Huge collaborative work.
✅ 28 trials, 8.000+ pts, 7.6y FU
✅ more chemo (ind+conc or conc+adj) ➡️superior (OS/PFS) to CRT alone but more toxFree 50day link: https://t.co/BtRJDZERRZ pic.twitter.com/v2v5MsinnV
— Pierre Blanchard, MD (@PBlanchardMD) June 1, 2023
MASCC Guidelines for the prevention and management of acute radiation dermatitis | Part 1 – Systematic review
29 May, 2023 | 10:53h | UTCRelated:
RCT | Bacterial decolonization for prevention of radiation dermatitis
RCT | Mepitel film for the prevention of acute radiation dermatitis in breast cancer.
RCT | Bacterial decolonization for prevention of radiation dermatitis
8 May, 2023 | 12:46h | UTCBacterial Decolonization for Prevention of Radiation Dermatitis: A Randomized Clinical Trial – JAMA Oncology (free for a limited period)
News Release: A Simple Antibacterial Treatment Solves a Severe Skin Problem Caused by Radiation Therapy – Montefiore Einstein Cancer Center
Commentary on Twitter
Rand trial of 75 pts w/breast cancer + 2 with head/neck cancer showed no pts treated w/bacterial decolonization (BD) developed >gr 1 acute rad'n dermatitis (ARD), vs 24% of pts treated with standard of care, suggesting BD may be preventive vs ARD. https://t.co/6FAFH9kMt1 #RadOnc
— JAMA Oncology (@JAMAOnc) May 4, 2023
ASTRO/ESTRO Guideline | Treatment of oligometastatic non-small cell lung cancer
4 May, 2023 | 13:44h | UTC
Commentary on Twitter
ASTRO & ESTRO partnered to issue the first guideline on local therapy for oligometastatic lung cancer, out today in #PracticalRadOnc https://t.co/ZiM2RWX394 @ESTRO_RT @IyengarPuneeth @Mat_Guc pic.twitter.com/5DV3fRdn1o
— ASTRO (@ASTRO_org) April 25, 2023
AUA/SUO Guideline | Updates to Advanced Prostate Cancer
2 May, 2023 | 13:46h | UTCUpdates to Advanced Prostate Cancer: AUA/SUO Guideline (2023) – The Journal of Urology
Consensus Paper | Management of pathological thoracolumbar vertebral fractures in patients with multiple myeloma
25 Apr, 2023 | 14:11h | UTC
RCT | Stereotactic radiosurgery vs. conventional radiotherapy for localized vertebral metastases of the spine
24 Apr, 2023 | 13:37h | UTCStereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial – JAMA Oncology (link to abstract – $ for full-text)
Audio interview: Radiosurgery of Spine Metastasis—NRG/RTOG 0631 RCT Final Results – JAMA
Commentary on Twitter
Phase 3 rand trial of spinal radiosurgery vs. conventional external beam radiation therapy for pts w/spinal metastases showed radiosurgery did not significantly improve pain response at 3mo but showed feasibility that makes it widely used today. https://t.co/LvZY1nbUpS #RadOnc
— JAMA Oncology (@JAMAOnc) April 20, 2023
RCT | MRI–guided vs CT–guided stereotactic body radiotherapy for prostate cancer
18 Apr, 2023 | 12:52h | UTC
Phase 2 RCT | Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer
10 Apr, 2023 | 13:41h | UTCAddition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial – JAMA Oncology (free for a limited period)
Commentary on Twitter
Randomized trial of intermittent hormone therapy +/- radiation to oligometastatic sites of #prostatecancer shows significantly improved PFS & assoc time off hormone therapy & w/normal testosterone from combination. https://t.co/ZnmkQuqHZm #RadOnc #PCSM #GUCSM
— JAMA Oncology (@JAMAOnc) April 6, 2023
RCT | Effects of Docetaxel as a radiosensitizer in patients with head and neck cancer, unsuitable for cisplatin-based chemoradiation
29 Mar, 2023 | 13:05h | UTCResults of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation – Journal of Clinical Oncology (link to abstract – $ for full-text)
Editorial: Good Radiosensitizer Hunting – Journal of Clinical Oncology
Commentaries:
Docetaxel Added to Radiation Provides DFS, OS Benefit in Cisplatin-Ineligible HNSCC – OncLive
RCT | Hyperfractionation vs. standard fractionation in IMRT for patients with locally advanced recurrent nasopharyngeal carcinoma
22 Mar, 2023 | 13:12h | UTCHyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial – The Lancet (link to abstract – $ for full-text)