Oncology

Systematic review finds heterogeneous gonadal toxicity across non-breast solid cancers.

This systematic review of 102 studies assessed gonadal toxicity and fertility outcomes after GI cancers, sarcoma, lung cancer, and melanoma treatments. Evidence was highly heterogeneous, mostly observational, and therefore imprecise for guiding universal fertility-preservation protocols. Sarcoma regimens containing alkylating or platinum agents and pelvic radiotherapy were associated with higher risk of persistent gonadal failure. Melanoma survivors commonly retained fertility, though rare immune checkpoint inhibitor-related orchitis or azoospermia were reported. 1

Off-protocol radiotherapy is allowed but poorly specified in metastatic NSCLC systemic trials.

Among 79 prospective systemic therapy trials, 93.7% allowed pre-enrollment radiation and 8.9% prohibited off-protocol radiation. Only 21.5% required a radiation–drug washout and no trial detailed allowable dose, fractionation, or organ-at-risk constraints for off-protocol RT. No study reported actual off-protocol radiotherapy use or adjusted outcomes for it in analyses. Radiotherapy allowance was not significantly associated with trial positivity, but inconsistent reporting limits interpretability. 2

Longitudinal tumor-size modeling identifies mutations linked to treatment response in NSCLC.

Using an Andersen–Gill tumor-dynamics model on ~17,000 radiology reports, authors linked somatic mutations to recurrent tumor-size changes during treatment. They identified 27 mutations with differential treatment responses; deletions in MYBL1 and GATA3 validated in an external EGFR-TKI screen reaching Bonferroni significance. Thirteen mutations associated with differential progression or response were not detected by conventional PFS or OS models. Findings suggest longitudinal size dynamics can generate candidate gene–treatment interactions for future prospective validation. 3