Approach to radiation therapy in the Jehovah's Witness patient: An overview.

Jehovah's Witnesses are well-known in the medical community for their inability to accept blood products. Novel methods of treatment are often needed to avoid anemia and hematologic toxicity as inability to receive blood products may increase the risk of treatment related complications. We provide an overview of radiation treatment for Jehovah's Witness patients with an emphasis on bone marrow sparing strategies with intensity modulated radiation therapy (IMRT) to minimize hematologic toxicity.

Enhanced dermatologic toxicity following concurrent treatment with palbociclib and radiation therapy: A case report.

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitors represent a new class of targeted therapy options for the treatment of estrogen receptor-positive (ER+) human epidermal growth factor 2-negative (HER2-) metastatic breast cancer. There are currently no published prospective data on the safety of use of radiation treatment with palbociclib. CASE: We describe the case of a patient with metastatic breast cancer who received radiation treatment to a metastatic supraclavicular lymph node to planned 60 Gy in 30 fractions while on palbociclib, a selective inhibitor of CDK4/6. The patient developed early radiation toxicities including esophagitis and dermatitis that progressed to a severe left neck skin breakdown in the radiation field, resulting in the need for hospitalization. She had a break in treatment but was able to finish the radiation without palbociclib. Her tumor responded well to the treatment and her side effects healed. DISCUSSION: To our knowledge this is the first case to report on concurrent palbociclib and radiation use, with resultant enhanced radiation effects that required hospitalization for symptom management. Several preclinical studies have shown synergistic effects of radiation and both in vivo and in vitro experiments resulting in improved survival and decreased cell proliferation, respectively, through enhanced G1 cell cycle arrest. CONCLUSION: This case highlights the importance of using caution when combining radiation with the new targeted therapies. Until more data becomes available, physicians are recommended to exercise clinical judgment when deciding on whether to continue or discontinue a CDK4/6 inhibitor in a patient who may need radiation.

Prognostic impact of biologically equivalent dose in stereotactic body radiotherapy for renal cancer.

Purpose /Objectives Materials/Methods: The National Cancer Database (NCDB) was queried (2004-2017) for patients with RCC who did not have surgical resection but received definitive SBRT. Kaplan-Meier analysis with log-rank test was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using cox proportional hazard models to determine prognostic factors for OS. Results: A total of 344 patients with median age 77 (IQR 70-85) were included in this study. Median BED3 was 180 Gy (IQR 126.03-233.97). Median OS was 90 months in the highest quartile compared to 36-52 months in the lower three quartiles (p < 0.01). On UVA, the highest BED3 quartile was a positive prognostic factor (HR 0.67, p < 0.01 CI 0.51-0.91) while age, tumor size, T-stage, metastasis, renal pelvis location, and transitional cell histology were negative factors. On MVA, the highest BED3 quartile was remained significant (HR 0.69, p = 0.02; CI 0.49-0.95) as a positive factor, while age, metastasis were negative factors. Conclusion: Higher BED may be associated with improved OS. Prospective investigation is needed to clearly define optimal BED for SBRT used to treat RCC.

Contemporary trends in management of uveal melanoma.

Purpose: In the management of uveal melanoma, eye plaque brachytherapy (EPBT) has replaced enucleation as the standard of care for small size tumors that require treatment, and for medium size tumors. In the modern era, EPBT is being utilized more frequently for certain large tumors as well. While there is prospective randomized evidence to support utilization of EPBT for tumors of appropriate dimensions, it is unclear what the actual practice patterns are across the United States. The purpose of this publication was to look at contemporary trends in the management of uveal melanoma across the United States to determine whether practices are appropriately adopting EPBT, and to investigate demographic and socio-economic factors that might be associated with deviations from this standard of care. Material and methods: The National Cancer Database was queried (2004-2015) for patients with uveal melanoma. Data regarding tumor characteristics and treatment were collected. Two-sided Pearson χ2 test was used to compare categorical frequencies between patients who received globe preserving treatments vs. those who received enucleation. Multivariable logistic regression modeling was used to determine characteristics predictive for receiving enucleation. Results: The enucleation rate for small/medium tumors (≤ 10 mm apical height and ≤ 16 mm basal diameter) decreased from 20% in 2004 to 10% in 2015. The EPBT rate for large tumors increased from 30% in 2004 to 45% in 2015. Numerous demographic and socio-economic factors were found to be associated with higher rates of enucleation. Conclusions: The overall trend across the nation is a decreased enucleation rate for small/medium tumors, and an increased EPBT rate for large tumors. A fraction of patients who should be candidates for EPBT are instead receiving enucleation, and in this study, we have shown that certain adverse demographic factors are associated with this.

Time Interval to Initiation of Whole-Brain Radiation Therapy in Patients With Small Cell Lung Cancer With Brain Metastasis.

PURPOSE: Patients with small cell lung cancer (SCLC) who have brain metastases require whole-brain radiation therapy (WBRT). When there is no emergent indication for WBRT, patients may receive systemic therapy first and WBRT afterward. In scenarios when systemic therapy is initiated first, it has not been previously investigated whether delaying WBRT is harmful. METHODS AND MATERIALS: The National Cancer Database was queried (2004-2016) for patients with SCLC with brain metastases who received 30 Gy in 10 fractions of WBRT. Patients were divided into groups based on whether they received early WBRT (3-14 days after initiation of chemotherapy) or late WBRT (15-90 days after initiation of chemotherapy). Demographic and clinicopathologic categorical variables were compared between those who had early WBRT (3-14 days) and those who had late WBRT (15-90 days). Factors predictive for late WBRT were determined. Overall survival (OS), which was defined as days from diagnosis to death, was evaluated and variables prognostic for OS were determined. RESULTS: A total of 1082 patients met selection criteria; 587 (54%) had early WBRT and 495 (46%) received late WBRT. Groups were similarly distributed aside from days from initiating chemotherapy to initiating WBRT (P < .001). The early WBRT group had a median of 7 days (interquartile range [IQR], 5-10 days) from initiating chemotherapy to initiating WBRT and the late WBRT group had a median of 34 days (IQR, 21-57 days). On binary logistic regression analysis, a longer time interval between diagnosis and the start of systemic therapy was predictive for later WBRT. Median OS was 8.7 months for early WBRT and 7.5 months for late WBRT (hazard ratio [HR], 1.165; P = .008). Early WBRT (P = .02), female sex (P = .045), and private insurance (P = .04) were favorable prognostic factors for OS on multivariable analysis, whereas older age (P = .006) was an unfavorable prognostic factor. CONCLUSIONS: Patients with SCLC and brain metastases who received early WBRT were found to have a modest improvement in OS compared with patients who received late WBRT. These findings suggest that early WBRT should be offered to patients who have brain metastases, even in the absence of an indication for emergent WBRT.

Prognostic impact of radiation therapy in tubular carcinoma of the breast.

PURPOSE: Tubular carcinoma (TC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for TC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with TC remains unclear. MATERIALS AND METHODS: The National Cancer Database was queried (2004-2015) for patients with pN0M0 TC who underwent lumpectomy. Chi-square testing compared categorized variables between those who did and did not receive radiotherapy. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analysis identified variables prognostic for OS. Patients were divided into age cohorts ≤60 years and >60 years. Propensity score matching (PSM) was utilized to create similar cohorts. RESULTS: 9705 patients met selection criteria; 6182 (75.1%) received radiotherapy while 2045 (24.9%) did not. After PSM, radiotherapy (HR 0.582; 95% CI 0.494-0.686) and endocrine therapy (HR 0.737; 95% CI 0.623-0.872) were favorable prognostic factors on multivariate Cox regression analysis while age > 60 years (HR 5.131; 95% CI 3.753-7.016), Black race (HR 1.445; 95% CI 1.016-2.055), and Charlson-Deyo comorbidity score > 0 (HR 1.708; 95% CI 1.403-2.079) were unfavorable prognostic factors. After PSM, 5-year OS was 91.7% for those who received radiotherapy and 84.5% for those who did not; 10-year OS was 76.1% and 64.1%, respectively (p < 0.001). CONCLUSION: This is the largest study to date on TC and the prognostic impact of adjuvant radiotherapy. Postoperative radiotherapy is a favorable prognostic factor for OS in patients with pN0M0 TC, suggesting adjuvant radiotherapy should remain standard of care in these patients.

Eye plaque brachytherapy versus enucleation for ocular melanoma: an analysis from the National Cancer Database.

PURPOSE: There is no current randomized data comparing the efficacy of brachytherapy and enucleation for patients with larger sized tumors. The purpose of the present study was to use a large, contemporary database to determine current practice patterns and compare survival outcomes between different management options for patients with choroidal melanoma of various sizes. MATERIAL AND METHODS: The National Cancer Database was queried (2004-2014) for histologically-confirmed choroidal melanoma for patients treated with brachytherapy versus enucleation. Chi-square test was used to compare categorized demographic and clinical variables in both arms. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazards assessment determined variables associated with OS. Patients were divided into cohorts representing small, medium, and large tumors. Propensity scores matching (PSM) was utilized to compare more similar cohorts. RESULTS: A total of 7,096 patients met the selection criteria; 5,501 (78%) patients received brachytherapy and 1,595 (22%) patients were treated with enucleation. After PSM, 5-yr OS for small tumors was 87% vs. 64%, for medium tumors was 77% vs. 57%, and for large tumors was 68% vs. 46% for brachytherapy and enucleation, respectively (p < 0.001). Following PSM, multivariate Cox regression found older age (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.51-2.06), more comorbidities (HR = 1.46, 95% CI = 1.25-1.70), extraocular extension (EOE) (HR = 1.25, 95% CI = 1.06-1.48), ciliary body invasion (CBI) (HR = 1.20, 95% CI = 1.02-1.40), and larger size (HR = 1.52, 95% CI = 1.40-1.66) were negative prognosticators of survival. Brachytherapy was a positive prognosticator of survival (HR = 0.45, 95% CI = 0.40-0.51). CONCLUSIONS: Patients selected for brachytherapy had improved survival compared to enucleation in all size cohorts. EOE and CBI are significantly higher in the enucleation cohort and are important negative prognosticators for survival selected against patients having brachytherapy. Brachytherapy is a reasonable treatment option for certain patients with large size tumors.

Three-dimensional imaging assessment of anatomic invasion and volumetric considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx cancer.

OBJECTIVES: To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies. MATERIALS AND METHODS: The pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes. RESULTS: The median TV was 6.6 cm3. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis. CONCLUSION: The extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.

Quantitative pretreatment CT volumetry: Association with oncologic outcomes in patients with T4a squamous carcinoma of the larynx.

BACKGROUND: The purpose of this study was to determine the impact of CT-determined pretreatment primary tumor volume on survival and disease control in T4a laryngeal squamous cell carcinoma (SCC). METHODS: We retrospectively reviewed 124 patients with T4a laryngeal cancer from 2000-2011. Tumor volume measurements were collected and correlated with outcomes. RESULTS: Five-year overall survival (OS) for patients with tumor volume ≥21 cm3 treated with larynx preservation (n = 26 of 41) was significantly inferior compared to <21 cm3 (42% vs 64%, respectively; P = .003). Five-year OS for patients with tumor volumes ≥21 cm3 in the cohort treated with total laryngectomy followed by radiotherapy (RT; n = 42 of 83) was not statistically significant when compared to <21 cm3 (50% vs 63%, respectively; P = .058). On multivariate analysis, tumor volume ≥21 cm3 was a significant independent correlate of worse disease-specific survival (DSS; P = .004), event-free survival (P = .005), recurrence-free survival (RFS; P = .04), noncancer cause-specific survival (P = .02), and OS (P = .0002). CONCLUSION: Pretreatment CT-based tumor volume is an independent prognostic factor of outcomes in T4a laryngeal cancer.

Quantitative body mass characterization before and after head and neck cancer radiotherapy: A challenge of height-weight formulae using computed tomography measurement.

OBJECTIVES: We undertook a challenge to determine if one or more height-weight formula(e) can be clinically used as a surrogate for direct CT-based imaging assessment of body composition before and after radiotherapy for head and neck cancer (HNC) patients, who are at risk for cancer- and therapy-associated cachexia/sarcopenia. MATERIALS AND METHODS: This retrospective single-institution study included 215 HNC patients, treated with curative radiotherapy between 2003 and 2013. Height/weight measures were tabulated. Skeletal muscle mass was contoured on pre- and post-treatment CT at the L3 vertebral level. Three common lean body mass (LBM) formulae (Hume, Boer, and James) were calculated, and compared to CT assessment at each time point. RESULTS: 156 patients (73%) had tumors arising in the oropharynx and 130 (61%) received concurrent chemotherapy. Mean pretreatment body mass index (BMI) was 28.5±4.9kg/m(2) in men and 27.8±8kg/m(2) in women. Mean post-treatment BMI were 26.2±4.4kg/m(2) in men, 26±7.5kg/m(2) in women. Mean CT-derived LBM decreased from 55.2±11.8kg pre-therapy to 49.27±9.84kg post-radiation. Methods comparison revealed 95% limit of agreement of ±12.5-13.2kg between CT and height-weight formulae. Post-treatment LBM with the three formulae was significantly different from CT (p<0.0001). In all instances, no height-weight formula was practically equivalent to CT within±5kg. CONCLUSION: Formulae cannot accurately substitute for direct quantitative imaging LBM measurements. We therefore recommend CT-based LBM assessment as a routine practice of head and neck cancer patient body composition.

Magnetic resonance imaging of swallowing-related structures in nasopharyngeal carcinoma patients receiving IMRT: Longitudinal dose-response characterization of quantitative signal kinetics.

BACKGROUND: We aim to characterize serial (i.e., acute and late) MRI signal intensity (SI) changes in dysphagia-associated structures as a function of radiotherapy (RT) in nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: We retrospectively extracted data on 72 patients with stage III-IV NPC treated with intensity-modulated RT (IMRT). The mean T1- and T2-weighted MRI SIs were recorded for the superior pharyngeal constrictor (SPC) and soft palate (SP) at baseline, early-after IMRT, and last follow up, with normalization to structures receiving <5 Gy. RESULTS: All structures had a significant increase in T2 SIs early after treatment, irrespective of the mean dose given. At last follow-up, the increase in T2 SI subsided completely for SPC and partially for SP. The T1 SI did not change significantly in early follow-up images of both structures; on late follow-up, patients with mean doses >62.25 Gy had a significant decrease in the corresponding T1 SI for SPC (1.6 ± 0.4 vs. 1.3 ± 0.4, P=0.007) but decreased non-significantly for SP. CONCLUSIONS: Serial MRI acquisitions enable the identification of both early and late radiation-induced changes in swallowing structures after definitive IMRT for NPC. Dose dependent decrease in late T1 SI is associated with higher RT doses to the superior pharyngeal constrictor muscle; while dose independent increase in SI for both structures in early post-RT T2 images is observed and subsides after therapy. Further efforts will seek to elucidate the relationship between dose-dependent muscle SI changes and functional alteration of swallowing muscles.