Isolated progression of metastatic lung cancer: Clinical outcomes associated with definitive radiotherapy.

BACKGROUND: Progressive, metastatic non-small cell lung cancer (NSCLC) often requires the initiation of new systemic therapy. However, in patients with NSCLC that is oligoprogressive (≤3 lesions), local radiotherapy (RT) may allow for the eradication of resistant microclones and, therefore, the continuation of otherwise effective systemic therapy. METHODS: Patients treated from 2008 to 2019 with definitive doses of RT to all sites of intracranial or extracranial oligoprogression without a change in systemic therapy were identified. Radiographic progression-free survival (rPFS) and time to new therapy (TNT) were measured. Associations between baseline clinical and treatment-related variables were correlated with progression-free survival via Cox proportional hazards modeling. RESULTS: Among 198 unique patients, 253 oligoprogressive events were identified. Intracranial progression occurred in 51% of the patients, and extracranial progression occurred in 49%. In the entire cohort, the median rPFS was 7.9 months (95% CI, 6.5-10.0 months), and the median TNT was 8.8 months (95% CI, 7.2-10.9 months). On adjusted modeling, patients with the following disease characteristics were associated with better rPFS: better performance status (P = .003), fewer metastases (P = .03), longer time to oligoprogression (P = .009), and fewer previous systemic therapies (P = .02). Having multiple sites of oligoprogression was associated with worse rPFS (P < .001). CONCLUSIONS: In select patients with oligoprogression, definitive RT is a feasible treatment option to delay the initiation of next-line systemic therapies, which have more limited response rates and efficacy. Further randomized prospective data may help to validate these findings and identify which patients are most likely to benefit.

Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact.

BACKGROUND: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized. METHODS: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and any hospitalization, number of hospitalizations, and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively. RESULTS: Of 270 patients included: median age was 66.6 years (31-88), 50.4% of patients were male (n = 136), 62% were Caucasian (n = 168). Cancer-related hospitalization incidence was 17% (n = 47), of which 21% of patients hospitalized (n = 10/47) had > 1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of any hospitalization (95% confidence interval (CI) 1.2-5.0, P = 0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin > 10 (95% CI 1.3-5.4, P = 0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.02-3.1, P = 0.04). CONCLUSIONS: Our data show baseline factors can predict those who may be at increased risk for hospitalization, which was independently associated with increased mortality. Taken together, these data support the need for developing further studies aimed at early and aggressive interventions to decrease hospitalizations during treatment.

Porphyria cutanea tarda exacerbation as a paraneoplastic syndrome in vaginal cancer resolved with chemoradiation.

Porphyria Cutanea Tarda (PCT) is a rare paraneoplastic syndrome. The effects of therapeutic ionizing radiation in patients with PCT are not well understood. We report the case of a 55 year-old woman with a past medical history significant for kidney transplant with rejection and removal on hemodialysis, Stevens-Johnson syndrome, porphyria cutanea tarda, undifferentiated connective tissue disease probably systemic lupus, and hepatitis C, who underwent curative chemoradiation treatment for a recurrent vaginal squamous cell carcinoma. There was no increased acute toxicity and active porphyria cutanea tarda improved over the course of radiation treatment and fully resolved within 1 year. However, there was significant myofibrotic late toxicity within the treated region.

Longitudinal Trends of Financial Toxicity in Patients With Lung Cancer: A Prospective Cohort Study.

BACKGROUND: Cancer therapy is associated with severe financial burden. However, the magnitude and longitudinal patient relationship with financial toxicity (FT) in the initial course of therapy is unclear. METHODS: Patients with stage II-IV lung cancer were recruited in a prospective longitudinal study between July 2018 and March 2020. FT was measured via the validated COmprehensive Score for financial Toxicity (COST) at the time of cancer diagnosis and at 6-month follow-up (6MFU). 6MFU data were compared with corresponding baseline data. A lower COST score indicates increased financial hardship. RESULTS: At the time of analysis, 215 agreed to participate. Subsequently, 112 patients completed 6MFU. On average, slightly more FT was observed at diagnosis compared with 6MFU (median COSTbase 25 v COST6M 27; P < .001); however, individual patients experienced large changes in FT. At 6MFU, 27.7% of patients had made financial sacrifices to pay for treatment but only 4.5% refused medical care based on cost. Median reported out-of-pocket (OOP) costs for the initial 6 months of cancer treatment was $2,496 (range, $0-25,900). Risk factors for FT at diagnosis were unique from risk factors at 6MFU. Actual OOP expenses were not correlated with FT; however, inability to predict upcoming treatment expenses resulted in higher FT at 6MFU. DISCUSSION: FT is a pervasive challenge during the initiation of lung cancer treatment. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, resulting in unique interventional targets throughout therapy.

Neoadjuvant Chemoradiation Compared With Neoadjuvant Radiation Alone in the Management of High-Grade Soft Tissue Extremity Sarcomas.

PURPOSE: Patients with large, high-grade soft tissue sarcomas are commonly treated with aggressive limb preservation regimens. This study aimed to assess cancer control outcomes of patients treated with neoadjuvant chemoradiation (CRT) compared with radiation therapy (RT) alone. METHODS: We reviewed records of patients with high-grade extremity or trunk soft tissue sarcomas ≥5 cm who were treated with neoadjuvant radiation with or without chemotherapy. Patient and disease characteristics were compared using t test and χ2 tests. Standardized mortality ratio weighted method was used to compare overall survival (OS), local control, and disease-free (DFS) survival. Acute radiation and surgical toxicity were reported. RESULTS: In the study, 64 patients (34 CRT and 30 RT) treated between 1997 and 2015 were analyzed. In the RT group compared with the CRT group, the patient population was older, with a median age of 65 versus 50 years (P < .001), and more likely to have cardiovascular disease (CVD; 30% vs 0%, P < .001). At a median follow-up of 41 months, after adjusting for propensity score of receiving RT, the 3-year LC was 87.3% versus 86.1%, DFS was 58.5% versus 56.6%, and OS was 75.6% versus 69.0% for the CRT and RT groups, respectively (P > .05). Acute dermatitis occurred in 18% versus 3% and surgical complications occurred in 32% versus 17% of CRT and RT patients, respectively. CONCLUSIONS: In this study, patients receiving RT alone were more likely to be older and have comorbid cardiovascular disease. When controlling for baseline differences, neoadjuvant CRT and RT provided similar rates of LC, DFS, and OS.

Applying Non-Homogeneous Dose Optimization to Improve Conventionally Fractionated Radiation Plan Quality in Patients with Non-Small Cell Lung Cancer.

PURPOSE: Nonhomogeneous dose optimization (NHDO) is exploited in stereotactic body radiation therapy (SBRT) to increase dose delivery to the tumor and allow rapid dose falloff to surrounding normal tissues. We investigate changes in plan quality when NHDO is applied to inverse-planned conventionally fractionated radiation therapy (CF-RT) plans in patients with non-small cell lung cancer. METHODS AND MATERIALS: Patients with near-central non-small cell lung cancer treated with CF-RT in 2018 at a single institution were identified. CF-RT plans were replanned using NHDO techniques, including normalizing to a lower isodose line, while maintaining clinically acceptable normal tissue constraints and target coverage. Tumor control probabilities were calculated. We compared delivered CF-RT plans using homogenous dose optimization (HDO) versus NHDO using Wilcoxon signed-rank tests. Median values are reported. RESULTS: Thirteen patients were replanned with NHDO techniques. Planning target volume coverage by the prescription dose was similar (NHDO = 96% vs HDO = 97%, P = .3). All normal-tissue dose constraints were met. NHDO plans were prescribed to a lower-prescription isodose line compared with HDO plans (85% vs 97%, P = .001). NHDO increased mean dose to the planning target volume (73 Gy vs 67 Gy), dose heterogeneity, and dose falloff gradient (P < .03). NHDO decreased mean dose to surrounding lungs, esophagus, and heart (relative reduction of 6%, 14%, and 15%, respectively; P < .05). Other normal tissue objectives improved with NHDO, including total lung V40 and V60, heart V30, and maximum esophageal dose (P < .05). Tumor control probabilities doubled from 31.6% to 65.4% with NHDO (P = .001). CONCLUSIONS: In select patients, NHDO principles used in SBRT optimization can be applied to CF-RT. NHDO results in increased tumor dose, reduction in select organ-at-risk dose objectives, and better maintenance of target coverage and normal-tissue constraints compared with HDO. Our data demonstrate that principles of NHDO used in SBRT can also improve plan quality in CF-RT.

Relationship Between Prior Radiotherapy and Checkpoint-Inhibitor Pneumonitis in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR) pneumonitis in non-small-cell lung cancer (NSCLC) patients treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). PATIENTS AND METHODS: Between June 2011 and July 2017, NSCLC patients treated with anti-PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. RESULTS: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3) months and median age 66 (range, 39-91) years; 54% (n = 102) were male; and 42% (n = 79) had stage I-III NSCLC at initial diagnosis. Patients received anti-PD-1/PD-L1 monotherapy (n = 127, 68%) or PD-1/PD-L1-based combinations (n = 61, 32%). In the entire cohort, 70% (132/188) received any RT, 53% (100/188) chest RT, and 37% (70/188) curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P = .051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. CONCLUSION: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti-PD-1/PD-L1 agents.

Adjuvant therapy after radical trachelectomy for stage I cervical cancer.

•Radical trachelectomy is a fertility sparing option for select stage I cervical patients.•Indications for adjuvant treatment following trachelectomy are based on standard recommendations following hysterectomy.•Case report outlining specifics of imaged-guided brachytherapy as part of the adjuvant treatment after trachelectomy.