What are the most recent updates to cancer guidelines, including changes to systemic therapy, radiation schemes (Stereotactic Body Radiation Therapy (SBRT) vs hypofractionated radiation), whole brain radiation therapy vs Stereotactic Radiosurgery (SRS), and TNM (Tumor, Node, Metastasis) staging, across all cancer types?

Recent Cancer Guideline Updates: Comprehensive Report

Critical Limitation of Available Evidence

The evidence provided is severely outdated (2012-2018), with the most recent guideline being from 2018, making it impossible to provide updates from the last 6-12 months as requested. The only exception is lung cancer TNM staging, where the 9th edition became effective January 1,2025 1, 2.

---

Lung Cancer: TNM Staging Updates (9th Edition - Effective January 2025)

Major Changes in N2 Classification

The most significant update is the subdivision of N2 mediastinal nodal disease into N2a (single-station involvement) and N2b (multiple-station involvement), reflecting distinct prognostic implications 1, 2.

• N2a: Single mediastinal lymph node station involvement 2
• N2b: Multiple mediastatic lymph node station involvement 2
• This reclassification allows for potential downstaging and expanded treatment options 1

M1c Metastatic Disease Subdivision

The M1c category is now subdivided into M1c1 (multiple metastases in a single organ system) and M1c2 (metastases in multiple organ systems) 1, 2.

• M1c1: Multiple extrathoracic metastatic lesions confined to a single organ system 2
• M1c2: Multiple extrathoracic metastatic lesions involving multiple organ systems 2
• This subdivision affects stage classification and treatment eligibility 1

Post-Neoadjuvant Staging Considerations

• Patients in the post-neoadjuvant ypN category demonstrate worse prognosis than those in the similar non-neoadjuvant pN category 2
• This distinction is critical for accurate prognostic assessment following neoadjuvant therapy 2

---

Brain Metastases: Radiation Therapy Updates (2014-2018)

Stereotactic Radiosurgery (SRS) Expansion

SRS is no longer limited to patients with 3 or fewer brain metastases; total disease burden (volume) rather than lesion number is now the primary selection criterion 3.

Volume-Based Selection Criteria

• Favorable outcomes: Total treatment volume <7 mL with <7 brain lesions (median survival 13 months vs 6 months) 3
• Alternative threshold: Total SRS-treated tumor volume <5 mL or 5-10 mL associated with longer survival compared to >10 mL 3
• Patients with >15 lesions have higher risk of developing new lesions and distant disease progression 3

Favorable Histologies for Multi-Lesion SRS

• Breast cancer patients with controlled primary tumors benefit from SRS regardless of number of brain metastases 3
• Radioresistant tumors (melanoma, renal cell carcinoma) achieve good local control with SRS 3
• Additional predictors of longer survival: younger age, good performance status, controlled primary tumor 3

SRS vs. Whole Brain Radiation Therapy (WBRT)

SRS Alone vs. SRS + WBRT

For patients with 1-4 brain metastases <3 cm, SRS alone preserves cognitive function compared to SRS + WBRT, with no survival difference 3.

• Adding WBRT to SRS does not prolong median survival (7.5 vs 8.0 months) 3
• WBRT + SRS reduces 1-year brain recurrence rate (47% vs 76%, P<.001) 3
• Critical caveat: SRS + WBRT causes significant decline in learning and memory function (52% vs 24% with SRS alone) 3

SRS + WBRT vs. WBRT Alone

• For single brain metastasis: SRS + WBRT improves survival (6.5 vs 4.9 months, P=.04) 3
• For 2-3 metastases: No survival benefit observed 3
• SRS addition significantly improves local control and performance status 3

HER2-Positive Breast Cancer with Brain Metastases (2018 ASCO Guidelines)

Single Brain Metastasis with Favorable Prognosis

Treatment options include surgery with postoperative radiation, SRS, WBRT, or SRS ± WBRT, depending on metastasis size, resectability, and symptoms 3.

• Serial imaging every 2-4 months for monitoring local and distant brain failure 3

Limited Metastases (2-4 Lesions) with Favorable Prognosis

• Resection for large symptomatic lesions plus postoperative radiotherapy 3
• SRS for additional smaller lesions 3
• WBRT ± SRS or SRS ± WBRT as alternatives 3
• Fractionated stereotactic radiotherapy (FSRT) for metastases 3-4 cm 3

Diffuse/Extensive Metastases

• WBRT may be offered for patients with more favorable prognosis 3
• WBRT for symptomatic leptomeningeal metastasis 3

Poor Prognosis Patients

• Options: WBRT, best supportive care, and/or palliative care 3

Systemic Therapy Coordination

• If systemic disease is NOT progressive at brain metastasis diagnosis: Do not switch systemic therapy 3
• If systemic disease IS progressive at brain metastasis diagnosis: Offer HER2-targeted therapy according to metastatic breast cancer algorithms 3

Surveillance Recommendations

• Do not perform routine surveillance brain MRI in patients without known history or symptoms of brain metastases 3
• Maintain low threshold for diagnostic brain MRI with any neurologic symptoms suggestive of brain involvement 3

---

Melanoma: Radiation Therapy and Systemic Therapy Updates (2012-2014)

Adjuvant Radiation Therapy for Regional Disease

Adjuvant nodal basin radiation therapy is recommended (Category 2B) for selected patients following resection of clinically appreciable nodes if LDH <1.5× upper limit of normal AND gross nodal extracapsular extension is present 3.

Additional Indications for Adjuvant RT

• Parotid region: ≥1 positive node 3
• Cervical or axillary region: ≥2 positive nodes 3
• Groin region: ≥3 positive nodes 3
• Maximum nodal diameter ≥3 cm (neck) or ≥4 cm (axilla/groin) 3

Evidence Base

• Regional recurrence: 10.2% with radiation vs 40.6% without radiation (5-year follow-up) 3
• Lymph node field recurrence significantly reduced (HR 0.56,95% CI 0.32-0.98, P=.041) 3
• Critical limitation: No impact on relapse-free or overall survival 3
• Important caveat: Increased probability of long-term skin and regional toxicities and potential reduced quality of life 3

Dose/Fractionation Considerations

• Wide range of radiation dose/fractionation schedules is effective 3
• Hypofractionated regimens may increase risk for long-term complications 3

Primary Disease Radiation Indications

• Adjuvant treatment for desmoplastic melanoma with narrow margins, locally recurrent disease, or extensive neurotropism 3

Systemic Therapy Options for Advanced/Metastatic Melanoma (2012)

Clinical trial participation is preferred 3.

First-Line Options

1. Ipilimumab (Category 1) 3

   • Potential for significant immune-mediated complications 3
   • Requires participation in REMS program and/or experience with the drug 3
   • Use with extreme caution in patients with serious underlying autoimmune disorders 3

2. Vemurafenib (Category 1) - for BRAF V600 mutations 3

   • BRAF mutations found in 56% of CSD melanomas vs 6% acral, 21% mucosal, 3% other 3

3. Dacarbazine 3

4. Temozolomide 3

5. High-dose interleukin-2 3

Alternative Regimens (Category 2B)

• Dacarbazine- or temozolomide-based combination chemotherapy/biochemotherapy 3
• Paclitaxel ± cisplatin or carboplatin 3

---

Radiation Therapy Combined with Immunotherapy (2021 Research)

SBRT/Hypofractionated RT with Anti-PD-1/PD-L1 Therapy

Stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy (HFRT) provides higher doses per fraction, achieving immune activation effects and overcoming tumor resistance to anti-PD-1/PD-L1 treatment 4.

Role Based on Metastatic Burden

• Oligometastatic disease: Radiotherapy as local radical treatment aiming to eliminate cancers in cooperation with systemic PD-1 inhibitors 4
• Bulky or multiple metastatic tumors: Radiotherapy as adjuvant to systemic immunotherapy 4

---

General SRS Technology Applications (2025 Praxis Medical Insights)

Tumor Control Rates by Indication

• Brain metastases: 94-100% tumor control (American College of Radiology recommendation) 5
• Benign intracranial meningiomas: 71-100% 10-year local control (Congress of Neurological Surgeons) 5
• Secretory pituitary adenomas: 92-97% tumor control (Endocrine Society) 5
• Arteriovenous malformations: 83-100% tumor control (American Association of Neurological Surgeons) 5
• Vestibular schwannomas: Approximately 96% tumor control (NCCN) 5

---

Summary of What Actually Changed

Definitive Recent Changes (2024-2025)

1. Lung Cancer TNM-9 (effective January 2025): N2 split into N2a/N2b; M1c split into M1c1/M1c2 1, 2

Historical Changes (2012-2018) - No Recent Updates Available

1. Brain Metastases SRS: Expansion from ≤3 lesions to volume-based criteria 3
2. Melanoma Adjuvant RT: Category 2B recommendation for high-risk regional disease 3
3. HER2+ Breast Cancer Brain Mets: Comprehensive algorithm for radiation selection 3

For updates within the last 6-12 months across other cancer types, current evidence sources (dated 2012-2018) cannot provide this information. Consultation of 2024-2025 NCCN, ASCO, ESMO, and other major society guidelines is required.