Clinical experience using a video-guided spirometry system for deep inhalation breath-hold radiotherapy of left-sided breast cancer.

The purpose was to report clinical experience of a video-guided spirometry system in applying deep inhalation breath-hold (DIBH) radiotherapy for left-sided breast cancer, and to study the systematic and random uncertainties, intra- and interfraction motion and impact on cardiac dose associated with DIBH. The data from 28 left-sided breast cancer patients treated with spirometer-guided DIBH radiation were studied. Dosimetric comparisons between free-breathing (FB) and DIBH plans were performed. The distance between the heart and chest wall measured on the digitally reconstructed radiographs (DRR) and MV portal images, dDRR(DIBH) and dport(DIBH), respectively, was compared as a measure of DIBH setup uncertainty. The difference (Δd) between dDRR(DIBH) and dport(DIBH) was defined as the systematic uncertainty. The standard deviation of Δd for each patient was defined as the random uncertainty. MV cine images during radiation were acquired. Affine registrations of the cine images acquired during one fraction and multiple fractions were performed to study the intra- and interfraction motion of the chest wall. The median chest wall motion was used as the metric for intra- and interfraction analysis. Breast motions in superior-inferior (SI) direction and "AP" (defined on the DRR or MV portal image as the direction perpendicular to the SI direction) are reported. Systematic and random uncertainties of 3.8 mm and 2mm, respectively, were found for this spirometer-guided DIBH treatment. MV cine analysis showed that intrafraction chest wall motions during DIBH were 0.3mm in "AP" and 0.6 mm in SI. The interfraction chest wall motions were 3.6 mm in "AP" and 3.4 mm in SI. Utilization of DIBH with this spirometry system led to a statistically significant reduction of cardiac dose relative to FB treatment. The DIBH using video-guided spirometry provided reproducible cardiac sparing with minimal intra- and interfraction chest wall motion, and thus is a valuable adjunct to modern breast treatment techniques.

Left Anterior Descending Coronary Artery Radiation Dose Association With All-Cause Mortality in NRG Oncology Trial RTOG 0617.

PURPOSE: A left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15 Gy) ≥10% has been recently observed to be an independent risk factor of major adverse cardiac events and all-cause mortality in patients with locally advanced non-small cell lung cancer treated with radiation therapy. However, this dose constraint has not been validated in independent or prospective data sets. METHODS AND MATERIALS: The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 0617 data set from the National Clinical Trials Network was used. The LAD coronary artery was manually contoured. Multivariable Cox regression was performed, adjusting for known prognostic factors. Kaplan-Meier estimates of overall survival (OS) were calculated. For assessment of baseline cardiovascular risk, only age, sex, and smoking history were available. RESULTS: There were 449 patients with LAD dose-volume data and clinical outcomes available after 10 patients were excluded owing to unreliable LAD dose statistics. The median age was 64 years. The median LAD V15 Gy was 38% (interquartile range, 15%-62%), including 94 patients (21%) with LAD V15 Gy <10% and 355 (79%) with LAD V15 Gy ≥10%. Adjusting for prognostic factors, LAD V15 Gy ≥10% versus <10% was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.43; 95% confidence interval, 1.02-1.99; P = .037), whereas a mean heart dose ≥10 Gy versus <10 Gy was not (adjusted HR, 1.12; 95% confidence interval, 0.88-1.43; P = .36). The median OS for patients with LAD V15 Gy ≥10% versus <10% was 20.2 versus 25.1 months, respectively, with 2-year OS estimates of 47% versus 67% (P = .004), respectively. CONCLUSIONS: In a reanalysis of RTOG 0617, LAD V15 Gy ≥10% was associated with an increased risk of all-cause mortality. These findings underscore the need for improved cardiac risk stratification and aggressive risk mitigation strategies, including implementation of cardiac substructure dose constraints in national guidelines and clinical trials.

Intracranial Activity of Cabozantinib in MET Exon 14-Positive NSCLC with Brain Metastases.

INTRODUCTION: A significant portion of NSCLCs with MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping alterations are sensitive to small-molecule mesenchymal-epithelial transition tyrosine kinase inhibitors. However, the incidence and management of brain metastases in this molecular subset is unknown and represents an unmet clinical need. METHODS: Hybrid capture-based comprehensive genomic profiling identified a patient with a MET exon 14 skipping alteration, and serial magnetic resonance imaging was utilized to follow intracranial disease during crizotinib and subsequent cabozantinib therapy. RESULTS: Intracranial progression developed in the context of ongoing extracranial disease control during crizotinib therapy. Rapid intracranial response was observed after change to cabozantinib. CONCLUSIONS: This report provides the first detailed description of brain metastases in MET exon 14-positive NSCLC and provides preliminary support for the intracranial activity of cabozantinib. Prospective study is warranted and needed to refine the management of intracranial disease in MET exon 14-positive NSCLC.

The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors.

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.

Wedge resection and brachytherapy for lung cancer in patients with poor pulmonary function.

BACKGROUND: Although lobectomy is the standard for lung cancer because a wedge resection has a 3 to 5 times greater incidence of local recurrence, poor pulmonary function may preclude lobectomy. For these patients, low-dose-rate brachytherapy has recently been used to decrease local recurrence after sublobar resection. Current techniques expose operating room personnel and patient contacts to unnecessary radioactivity risks. We present our technique of sublobar resection combined with afterload catheters for high-dose-rate brachytherapy for patient benefit with minimal risk to others. METHODS: Forty-eight patients (25 women, 23 men) underwent wedge resection, node dissection, and brachytherapy. A remote-afterloading high-dose-rate unit for radiation produced a median dose of 2450 cGy (350 cGy per fraction over 7 fractions twice daily for 4 days). The dose was prescribed to 1 cm deep to the stapled line. Biologically, this dose is approximately 5000 cGy and above (180 cGy/d equivalent) at the depth of 5 mm in reference to the resection margin. RESULTS: Two patients died. The length of mean stay was 5.5 days (median, 5 days). Complications included prolonged air leak in 5 patients, atrial fibrillation in 5, pneumonia in 3, trapped lung in 2, and 1 each with empyema, bleeding, and recurrent laryngeal nerve injury. Three patients required a blood transfusion. Within the follow-up of 1 to 27 months, there were four recurrences. CONCLUSIONS: Wedge resection and brachytherapy appears to be a reasonable treatment for patients with lung cancer and pulmonary function that prohibits a lobectomy.