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Radiation boost for ductal carcinoma in situ (August 2022)
The use of a radiation boost to the surgical bed reduces recurrences in patients receiving whole breast radiation therapy (WBRT) for early invasive breast cancer, but its role in ductal carcinoma in situ (DCIS) is less clear. In a randomized trial in over 1600 patients with DCIS with at least one risk feature, those assigned to a radiation boost experienced five-year free-from-local-recurrence rates of 97 versus 93 percent in the no boost group (hazard ratio 0.47) [1]. For most women receiving WBRT for early breast cancer including DCIS, we suggest radiation therapy boost to the tumor bed to reduce the risk of local recurrence.
Gemcitabine plus cisplatin in locally advanced nasopharyngeal carcinoma (August 2022)
For patients with locally advanced nasopharyngeal carcinoma (LANPC), induction chemotherapy with gemcitabine plus cisplatin followed by chemoradiation is the standard of care, but long-term follow-up of overall survival (OS) was not previously reported. In the final analysis of a phase III trial of almost 500 patients with newly diagnosed LANPC, the addition of induction chemotherapy with gemcitabine plus cisplatin to chemoradiation improved five-year OS (88 versus 79 percent) and did not worsen late toxicities [2]. Based on these data, for patients with LANPC who are candidates for induction chemotherapy, we continue to suggest the use of gemcitabine plus cisplatin over other regimens.
Crizotinib for ALK-positive inflammatory myofibroblastic tumor (August 2022)
Inflammatory myofibroblastic tumor (IMT) is a rare chemotherapy-resistant sarcoma, and there is interest in novel targeted therapies for patients with advanced disease. In two separate open-label phase I/II trials in patients with unresectable, recurrent, or refractory IMT harboring an ALK gene rearrangement, crizotinib demonstrated objective response rates of 86 percent among children (12 of 14 patients) and 71 percent among adults (5 of 7 patients) with no new toxicity signals [3]. Based on these data, the US Food and Drug Administration approved crizotinib for adult and pediatric patients with unresectable, recurrent, or refractory IMT harboring an ALK gene rearrangement, and we also suggest initial treatment with crizotinib in this population.
Prenatal cell-free screening results and maternal malignancy (August 2022)
In pregnant patients with a malignancy, noninvasive fetal aneuploidy screening with cell-free DNA (cfDNA) may detect circulating cfDNA from the tumor in addition to the usual placental and maternal cfDNA. In a study including over 168,000 pregnant patients who underwent prenatal genome-wide cfDNA screening, malignancy-suspicious results (ie, multiple chromosome imbalances) led to a new diagnosis of malignancy in 16 patients [4]. The appropriate clinical evaluation of malignancy-suspicious prenatal cfDNA results is unclear, in part because the results have no correlation with the tissue of origin of the malignancy. Patients undergoing prenatal fetal aneuploidy screening with a cfDNA test should be aware of the possibility of this rare incidental finding.
Vitamin D deficiency and risk for paclitaxel-related neuropathy (July 2022)
The predominant risk factor for paclitaxel-related peripheral sensory neuropathy (PSN) is cumulative dose over time; new data suggest that low vitamin D levels may contribute. In a retrospective analysis of data from the SWOG0221 trial comparing different paclitaxel-containing regimens for early-stage breast cancer, vitamin D levels <=20 ng/mL were associated with a higher PSN risk (19.3 versus 13.0 percent) [5]. Compared with White American patients, more Black American patients had vitamin D deficiency (78 versus 29 percent) and more developed treatment-related PSN (29.3 versus 13.3 percent). Adjusting for vitamin D deficiency decreased but did not eliminate the higher PSN risk in Black American patients. Although prospective trials are needed to test whether vitamin D supplementation lessens paclitaxel-related PSN, these data suggest that patients initiating treatment with paclitaxel should be screened for vitamin D deficiency and repleted, if levels are low.
1. Chua BH, Link EK, Kunkler IH, et al. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study. Lancet. 2022;400(10350):431.
2. Zhang Y, Chen L, Hu GQ, et al. Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial. J Clin Oncol. 2022;40(22):2420. Epub 2022 Jun 16.
3. Crizotinib: US Food and Drug Administration Prescribing Label https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/202570s033lbl.pdf (Accessed on July 18, 2022).
4. Heesterbeek CJ, Aukema SM, Galjaard RH, et al. Noninvasive Prenatal Test Results Indicative of Maternal Malignancies: A Nationwide Genetic and Clinical Follow-Up Study. J Clin Oncol. 2022;40(22):2426. Epub 2022 Apr 8.
5. Chen C-SC, Zirpoli G, McCann S, et al. Vitamin D insufficiency as a peripheral neuropathy risk factor in white and black patients in SWOG 0221 (abstract). J Clin Oncol. 40, 2022 (suppl 16; abstr 12023).
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