onc brain

ASTRO-convened think tank, February 2019, of physicians and scientists in genetic screening, genomics, radiosensitivity, risk estimation and clinical oncology. Narrative review with consensus points; no voting or agreement metrics reported.

Addresses pts with germline or somatic variants found on hereditary screening, direct-to-consumer CLIA testing, or tumor genomic panels. Panel recommends only CLIA-certified tests inform RT discussion and prefers paired tumor-normal sequencing.

VUS = normal. BRCA1/2: no excess RT toxicity or RT-induced second cancers, extended to PALB2, CHEK2, RAD50. Deleterious heterozygous ATM: avoid optional RT in young pts, close CBC screening after indicated RT. RB1, NF1, TP53, PTCH1 syndromes carry elevated in-field second malignancy risk.

Somatic ATM truncation tracked with improved local control after palliative RT (P < .001) without OS difference, read as an RT-specific effect. No tumor mutation is yet clinically actionable for dose.

NCCN guidance covers counseling for common germline mutations but gives little RT-specific risk information. REQUITE (~4400 pts, 8 countries) and the Radiogenomics Consortium are named as the routes to validated polygenic toxicity predictors.

The ATM absolute risk is a rough estimate built from a SEER baseline and one cohort's RR, not a measured carrier-specific rate. Most cited studies lack a no-RT control, so RT-attributable risk is often inferred.

Panel proposes future genomic-adjusted RT trials include a no-RT arm to separate prognostic from predictive value. Polygenic, not single-gene, predictors are expected to be what eventually becomes actionable.

ISRS physics guideline built on a PRISMA systematic review of PubMed 2009-2020 (81 papers plus 7 international guidelines) and a 10-question survey of 14 committee members, 100% completion.

Scope is SRS for brain metastases ≤1 cm in maximal diameter on Gamma Knife, CyberKnife and SRS-adapted LINACs. Platform mix of included papers: LINAC 21, mixed 21, GK 20, CK 2.

Requires sub-mm geometric accuracy, a ≤1 mm geometric tolerance on system-specific E2E tests, and dosimetric accuracy within 5%. MLC width of no more than 5 mm is called a prerequisite; no CTV margin is usually applied, and PTV margin use is left platform-dependent.

Defers small-field dosimetry and QA tolerances to AAPM TG142, TG198 and TG178 and IAEA TRS 483, and adopts the ICRU 91 GTV definition. The ISRS contribution is the small-target layer: imaging recency, slice thickness, contrast timing and margin trade-offs.

Survey reached no consensus on 3 of 10 questions, so several statements reflect unresolved practice variation. Commissioning, QA program design and platform-specific planning are explicitly out of scope, and several authors carry vendor ties.

The panel frames margin addition or omission as the most controversial variable for small mets: absolute necrosis risk at this size is low, so relative increases may matter less in absolute terms. Cumulative dose across repeat SRS sessions is flagged as an open, clinically relevant problem.

Case-based practice guideline sponsored by the Radiosurgery Society, built around two cases: 7 NSCLC brain mets treated with 20 Gy/1 fx, and a resected 3.5 cm cerebellar colon met given 27 Gy/3 fx postop. The source states no panel voting, evidence grading or agreement metric.

Suitable: 1-15 lesions, diameter ≤3 cm, volume ≤14 cc. Cautionary: >15 lesions, 3-6 cm or >14 cc, SCLC, nodular LMD. Unsuitable: >6 cm or classical LMD.

<2 cm: 20-24 Gy/1 fx; 2-4 cm: 27 Gy/3 fx or 30 Gy/5 fx; >4 cm: surgery, with multifraction SRS if inoperable. Intact-lesion target is GTV on contrast T1 with a 1-2 mm PTV (1 mm whenever possible) and no CTV. Postop target is the cavity CTV with a PTV typically 2 mm, delivered within 4 wk of surgery.

Single-fraction brain V12 of 5, 10, >15 cc carries ~10%, 15%, 20% symptomatic RN. For reirradiation the guide cites total brain EQD2 <120 Gy, cumulative cord EQD2 ≤70 Gy and at least 5 months between courses.

The guide builds on RTOG 9508 (WBRT + SRS vs WBRT) and on N107C/RTOG 1270 in the postop setting, which made SRS alone standard for 1-4 mets. It extends SRS beyond that population to up to 15 lesions, larger lesions via fractionation, and preoperative SRS.

The 15-lesion boundary rests on a prospective observational study and an MD Anderson trial terminated early and published only as an abstract. The preop SRS LMD advantage comes from initial studies, and the guide itself reports similar LC, distant brain failure and OS for pre- and postoperative SRS.

Volume may matter more than count: on MVA, tumor volume, KPS and histology predicted OS but lesion number did not. Integral brain dose is offered as the practical ceiling, where a 9-, 177- or 42-tumor burden yields an 8 Gy whole-brain dose depending on size. The guide calls SRS in SCLC an acceptable option but not yet the default.

Review drawing on MEDLINE and citation tracking of key reviews and editorials. Evidence streams: misdiagnosed-DCIS follow-up, recurrence after BCS, autopsy, risk factors, animal and mathematical models.

Untreated misdiagnosed DCIS progressed in 14–53% over 10+ yr. Pooled recurrence 22.5% CS alone, 8.9% CS+RT, 1.4% mastectomy. Autopsy median DCIS prevalence 8.9%.

Predates the low-risk DCIS active-surveillance trials (LORIS, COMET, LORD), which test directly the progression question this review could only estimate indirectly from misdiagnosed biopsies.

Recurrence after surgery may not reflect the untreated course and depends strongly on excision margins. Boyages subgroup rates are pooled across series, not randomized contrasts.

Authors conclude DCIS is a precursor of most invasive breast cancer but not all DCIS progresses in the medium term. The autopsy reservoir argument for overdiagnosis is weakened because modelling predicts that reservoir even if all DCIS progresses.