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Radiation Oncology

RCT: Comparing Perioperative Chemotherapy Alone to Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy in Resectable Gastric Cancer

14 Sep, 2024 | 18:23h | UTC

Background:

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.

    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.
  • 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.
    • Progression-Free Survival:
      • Median progression-free survival was similar between the groups (31 months vs. 32 months).
  • 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%).
  • 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.

Reference: Leong, T., et al. (2024). Preoperative Chemoradiotherapy for Resectable Gastric Cancer. The New England Journal of Medicine.  DOI: http://doi.org/10.1056/NEJMoa2405195

 

Network Meta-Analysis: Preoperative Chemoradiotherapy and Chemotherapy Equally Improve Survival in Esophagogastric Adenocarcinoma – JAMA Netw Open

17 Aug, 2024 | 19:21h | UTC

Study 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.

Reference: Ronellenfitsch U, Friedrichs J, Barbier E, et al. (2024). Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis. JAMA Network Open, 7(8), e2425581. DOI: 10.1001/jamanetworkopen.2024.25581.

 

RCT: Radiation therapy alone superior to chemoradiation in low-grade localized endometrial cancer recurrences

1 May, 2024 | 21:41h | UTC

This 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):

Ann H. Klopp et al. (Year). Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial. Journal of Clinical Oncology. DOI: 10.1200/JCO.23.01279

 

The Lancet Commission: Global projections and recommendations for managing the increasing burden of prostate cancer

27 Apr, 2024 | 18:42h | UTC

The 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:

James, N.D., Tannock, I., N’Dow, J., Feng, F., Gillessen, S., Ali, S.A., et al. (2024). The Lancet Commission on prostate cancer: planning for the surge in cases. The Lancet, 404(10052), 1-29. DOI: https://doi.org/10.1016/S0140-6736(24)00651-2.

Phase 2 RCT | Adding stereotactic body radiotherapy to immune checkpoint inhibitors fails to improve outcomes in solid tumor patients

9 Aug, 2023 | 15:28h | UTC

Checkpoint 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 | UTC

Upfront 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

 

RCT | Dysphagia-optimized intensity-modulated radiotherapy better preserves swallowing function in pharyngeal cancer patients

25 Jul, 2023 | 13:52h | UTC

Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial – The Lancet Oncology

Commentaries:

Dysphagia-Optimized vs Standard IMRT in Newly Diagnosed Patients With Head and Neck Cancer – The ASCO Post

Radiation approach improves swallowing in head, neck cancer – MDedge

 

Commentary on Twitter

 

Phase 2 Trial | The addition of immunotherapy to stereotactic ablative radiotherapy may enhance EFS in early-stage NSCLC

25 Jul, 2023 | 13:36h | UTC

Stereotactic 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

Post‐mastectomy radiotherapy for women with early breast cancer and one to three positive lymph nodes – Cochrane Library

Summary: Is X-ray treatment (radiotherapy) after removal of breast tissue (mastectomy) better than no X-ray treatment in women diagnosed with breast cancer that has spread to one to three armpit lymph nodes? – Cochrane Library

 

RCT | Brachytherapy alone sufficient for intermediate-risk prostate cancer, no FFP improvement with additional EBRT

7 Jul, 2023 | 16:06h | UTC

Effect 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)

News Release: Addition of EBRT to brachytherapy did not improve outcomes for men with intermediate-risk prostate cancer, brachytherapy alone remains standard of care – NRG Oncology

 

ESTRO-ACROP guideline | Recommendations on implementation of breath-hold techniques in radiotherapy

22 Jun, 2023 | 14:51h | UTC

ESTRO-ACROP guideline: Recommendations on implementation of breath-hold techniques in radiotherapy – Radiotherapy and Oncology

 

RCT | Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer

15 Jun, 2023 | 15:04h | UTC

Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial – The Lancet

 

M-A | Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy

5 Jun, 2023 | 13:29h | UTC

Role 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

 

MASCC Guidelines for the prevention and management of acute radiation dermatitis | Part 1 – Systematic review

29 May, 2023 | 10:53h | UTC

MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis: part 1) systematic review – eClinicalMedicine

Related:

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 | UTC

Bacterial 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

 

ASTRO/ESTRO Guideline | Treatment of oligometastatic non-small cell lung cancer

4 May, 2023 | 13:44h | UTC

Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline – Practical Radiation Oncology

News Release: ASTRO and ESTRO issue clinical guideline on local therapy for oligometastatic lung cancer – American Society for Radiation Oncology (ASTRO)

Commentary: ASTRO and ESTRO Issue New Clinical Guidelines on Local Therapy for Patients With Oligometastatic NSCLC – The ASCO Post

 

Commentary on Twitter

 

AUA/SUO Guideline | Updates to Advanced Prostate Cancer

2 May, 2023 | 13:46h | UTC

Updates 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

Management of Pathological Thoracolumbar Vertebral Fractures in Patients With Multiple Myeloma: Multidisciplinary Recommendations – Global Spine Journal

 

RCT | Stereotactic radiosurgery vs. conventional radiotherapy for localized vertebral metastases of the spine

24 Apr, 2023 | 13:37h | UTC

Stereotactic 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

 

RCT | MRI–guided vs CT–guided stereotactic body radiotherapy for prostate cancer

18 Apr, 2023 | 12:52h | UTC

Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial – JAMA Oncology

News Release: MRI-guided radiotherapy produces fewer side effects and better quality of life for patients with localized prostate cancer – University of California – Los Angeles Health Sciences

 

Phase 2 RCT | Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer

10 Apr, 2023 | 13:41h | UTC

Addition 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

 

RCT | Effects of Docetaxel as a radiosensitizer in patients with head and neck cancer, unsuitable for cisplatin-based chemoradiation

29 Mar, 2023 | 13:05h | UTC

Results 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

Docetaxel as a Radiosensitizer in Cisplatin-Ineligible Patients With Locally Advanced Head and Neck Cancer – The ASCO Post

 

RCT | Hyperfractionation vs. standard fractionation in IMRT for patients with locally advanced recurrent nasopharyngeal carcinoma

22 Mar, 2023 | 13:12h | UTC

Hyperfractionation 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)

Commentary: Hyperfractionated vs Standard-Fractionation IMRT in Locally Advanced, Recurrent Nasopharyngeal Carcinoma – The ASCO Post

 

RCT | Patient-reported outcomes 12 years after different treatments for localized prostate cancer

15 Mar, 2023 | 15:24h | UTC

Summary: The article reports on a study that evaluated patient-reported outcomes of 1,643 participants in the ProtecT trial over a period of 7 to 12 years to assess the long-term functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring for localized prostate cancer detected by PSA screening.

The study found that generic quality-of-life scores were similar among the randomized groups over 7 to 12 years. However, although the prostatectomy group had a lower incidence of nocturia, they showed a higher incidence of urinary incontinence and sexual dysfunction compared to the radiotherapy and active monitoring groups. The radiotherapy group had a higher incidence of fecal leakage compared to the other groups.

The study provides evidence that helps patients and their clinicians assess the trade-offs between treatment harms and benefits and make better-informed treatment decisions.

Article: Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment – NEJM Evidence

Original Study: RCT | Localized prostate cancer treatment options have similar 15-year survival outcomes

 

Dose‐escalated radiotherapy for clinically localized and locally advanced prostate cancer

14 Mar, 2023 | 13:21h | UTC

Dose‐escalated radiotherapy for clinically localized and locally advanced prostate cancer – Cochrane Library

Summary: Dose-escalated radiotherapy for curative treatment in men with clinically localized prostate cancer – Cochrane Library

 

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