Vitamin B12 and Folate Status in Head and Neck Cancer

Deficiency of vitamin B12 and folate is associated with causation of certain precancerous conditions and cancer.The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214head and neck cancer patients, to evaluate the plasma vitamin B12 and folate levels to determine their associationwith tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using ahealth habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B12and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower educationand low income were among the risk factors. A decrease in the plasma vitamin B12 and folate levels with respect totobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile forvitamin B12 and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly,the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts.There was a significant positive correlation between vitamin B12 and folate levels in the subjects consuming tobacco,and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advancedas compared with early disease (ANOVA p=0.006 and Spearman’s Rho = -0.211 and p=0.01). The results suggest,potential significance of plasma vitamin B12 and folate levels in head and neck malignancies which needs to beconfirmed by further studies on a large population.     

Is Planned Neck Dissection Necessary for Head and Neck Cancer After Intensity-Modulated Radiotherapy?

PURPOSE: The objective of this study was to determine regional control of local regional advanced head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT), along with the role and selection criteria for neck dissection after IMRT. METHODS AND MATERIALS: A total of 90 patients with stage N2A or greater HNSCC were treated with definitive IMRT from December 1999 to July 2005. Three clinical target volumes were defined and were treated to 70 to 74 Gy, 60 Gy, and 54 Gy, respectively. Neck dissection was performed for selected patients after IMRT. Selection criteria evolved during this period with emphasis on post-IMRT [(18)F] fluorodeoxyglucose positron emission tomography in recent years. RESULTS: Median follow-up for all patients was 29 months (range, 0.2-74 months). All living patients were followed at least 9 months after completing treatment. Thirteen patients underwent neck dissection after IMRT because of residual lymphadenopathy. Of these, 6 contained residual viable tumor. Three patients with persistent adenopathy did not undergo neck dissection: 2 refused and 1 had lung metastasis. Among the remaining 74 patients who were observed without neck dissection, there was only 1 case of regional failure. Among all 90 patients in this study, the 3-year local and regional control was 96.3% and 95.4%, respectively. CONCLUSIONS: Appropriately delivered IMRT has excellent dose coverage for cervical lymph nodes. A high radiation dose can be safely delivered to the abnormal lymph nodes. There is a high complete response rate. Routine planned neck dissection for patients with N2A and higher stage after IMRT is not necessary. Post-IMRT [(18)F] fluorodeoxyglucose positron emission tomography is a useful tool in selecting patients appropriate for neck dissection.     

How Much Radiation is the Chemotherapy Worth in Advanced Head and Neck Cancer?

PURPOSE: To estimate the radiotherapeutic dose equivalence of chemoradiotherapy in head and neck cancer. METHODS: The biologic equivalent dose (BED) of radiotherapy in nine trials of standard and five trials of modified fractionated radiotherapy with or without chemotherapy was calculated using the linear-quadratic formulation. Data from Radiation Therapy Oncology Group (RTOG) study 90-03 were used to calculate the relationship (S) between increase in locoregional control (LRC) and increase in BED with modified vs. standard fractionated radiotherapy. The increase in LRC with chemoradiotherapy vs. radiotherapy alone, the BED of the radiotherapy-alone arms, and the "S" value were used to calculate the BED contribution from chemotherapy and the total BED of chemoradiotherapy from each study. RESULTS: From RTOG 90-03, a 1% increase in BED yields a 1.1% increase in LRC. The mean BED of standard fractioned radiotherapy was 60.2 Gy(10) and 66 Gy(10) for modified fractionation. The mean BED of standard fractionated chemoradiotherapy was 71 Gy(10) (10.8 Gy(10) contributed by chemotherapy). The mean BED of modified fractionated chemoradiotherapy was 76 Gy(10) (10.4 Gy(10) contributed by chemotherapy). CONCLUSIONS: Chemotherapy increases BED by approximately 10 Gy(10) in standard and modified fractionated radiotherapy, equivalent to a dose escalation of 12 Gy in 2 Gy daily or 1.2 Gy twice daily. Such an escalation could not be safely achieved by increasing radiation dose alone.     

Single Institution Experience of Proton and Photon-based Postoperative Radiation Therapy for Non–small-cell Lung Cancer

IntroductionPostoperative radiation therapy (PORT) for non–small-cell lung cancer remains controversial with studies showing no overall survival (OS) benefit in the setting of excessive cardiopulmonary toxicity. Proton beam therapy (PBT) can potentially reduce toxicity with improved organ-at-risk sparing. We evaluated outcomes of PORT patients treated with PBT and intensity-modulated radiation therapy (IMRT).Materials and MethodsThis is a retrospective review of 136 PORT patients (61 PBT, 75 IMRT) treated from 2003 to 2016. A Kaplan-Meier analysis was performed to assess oncologic outcomes. A Cox regression was conducted to identify associated factors. Total toxicity burden (TTB) was defined as grade ≥ 2 pneumonitis, cardiac, or esophageal toxicity.ResultsMedian OS was 76 and 46 months for PBT and IMRT with corresponding 1- and 5-year OS of 85.3%, 50.9% and 89.3%, 37.2% (P = .38), respectively. V30 Gy heart (odds ratio [OR], 144.9; 95% confidence interval [CI], 2.91-7214; P = .013) and V5 Gy lung (OR, 15.8; 95% CI, 1.22-202.7; P = .03) were predictive of OS. Organ-at-risk sparing was improved with PBT versus IMRT; mean heart 2.0 versus 7.4 Gy (P < .01), V30 Gy heart 2.6% versus 10.7% (P < .01), mean lung 7.9 versus 10.4 Gy (P = .042), V5 Gy lung 23.4% versus 42.1% (P < .01), and V10 Gy lung 20.4% versus 29.6% (P < .01). TTB was reduced with PBT (OR, 0.35; 95% CI, 0.15-0.83; P = .017). Rates of cardiac toxicity were 14.7% IMRT and 4.9% PBT (P = .09). Rates of ≥ grade 2 pneumonitis were 17.0% IMRT and 4.9% PBT (P = .104).ConclusionPBT improved cardiac and lung sparing and reduced toxicity compared with IMRT. Considering the impact of cardiopulmonary toxicity on PORT outcomes, PBT warrants prospective evaluation.     

Recommendations for Single-Fraction Radiation Therapy and Stereotactic Body Radiation Therapy in Palliative Treatment of Bone Metastases: A Statewide Practice Patterns Survey

PurposeSingle-fraction (SF) radiation therapy is effective and convenient for patients with painful noncomplex bone metastases. Prior survey results reported a low recommendation of SF radiation therapy in the US. We sought to assess contemporary treatment recommendations for the management of bone metastases among diverse physicians participating in a statewide quality consortium.Methods and MaterialsMembers of the Michigan Radiation Oncology Quality Consortium were surveyed between April and May 2017. Physicians rated the importance of 31 variables on their choice of dose fractionation. The survey also covered 7 patient scenarios.ResultsFifty-six physicians responded who were practicing at 18 of 20 centers surveyed. Respondents recommended 23 dose-fractionation schedules across the 7 scenarios. Highest-rated factors considered when choosing a dose fractionation regimen were performance status, prognosis, spinal cord compression, and prior radiation therapy. Recommendations for SF overall were uncommon (16.1%). On multivariable analysis, factors associated with SF use included academic employment (odds ratio [OR] 2.04; 95% CI, 1.02-4.08; P = .044) and higher palliative case volume (OR 2.59; 95% CI, 1.45-4.63; P = .001). Stereotactic body radiation therapy (SBRT) was recommended in 16.4% of scenarios overall, and on multivariable analysis, significant predictors for SBRT use were academic employment (OR 2.99; 95% CI, 1.39-6.44; P = .005), more recent residency completion (OR 4.37; 95% CI, 1.26-15.17; P = .02), spine location (OR 12.54; 95% CI, 3.96-39.68; P < .001), and prior radiation therapy (OR 26.67; 95% CI, 7.86-90.57; P < .001). SF rates were higher than in a survey reported in 2009 (16.1% vs 9.4%, P = .0004).ConclusionsSF radiation therapy remains uncommonly recommended, although it may be recommended more now than it was 10 years ago despite the increased utilization of SBRT. We identify multiple key drivers in physician decision making affecting SF recommendations that have not been addressed by prior level one evidence. Further research with evidence-based recommendations to clarify the role of SF and SBRT in management of patients with bony metastases are needed.     

Early Mortality after Radical Radiotherapy in Head and Neck Cancer – A Nationwide Analysis from the Danish Head and Neck Cancer Group (DAHANCA) Database

AimsCurative-intent radiotherapy (RT) or chemoradiation (CRT) of squamous cell carcinoma of the head and neck (HNSCC) produces high survival rates, but is associated with substantial toxicity. However, there are no commonly accepted quality metrics for early mortality in radiation oncology. To assess the applicability of early mortality as a clinical quality indicator, this study investigated the temporal distribution, risk factors and trends of 90- and 180-day overall and non-cancer mortality in a nationwide cohort of HNSCC patients treated with RT/CRT.Materials and methodsInformation on all HNSCC patients treated with curative-intent RT/CRT in Denmark between 2000 and 2017 was obtained from the national Danish Head and Neck Cancer Group clinical database. Deaths in patients with residual or recurrent disease after RT/CRT were classified as cancer-related. Possible risk factors were investigated using logistic regression analysis.ResultsData from 11 419 patients were extracted. In total, 90- and 180-day mortality risks were 3.1% and 7.1%, respectively. There was a uniform temporal distribution of 180-day mortality. In multivariable analysis, increasing age, stage, performance status, earlier treatment year and hypopharyngeal cancer were significantly associated with an increased risk (P < 0.05). Risk factor estimates were comparable for 90- versus 180-day mortality as well as for overall versus non-cancer mortality. Between 2000 and 2017 there was a significant decrease in 180-day mortality, which was driven by a reduction in cancer-related events.ConclusionThe distribution of 180-day overall and non-cancer mortality did not indicate a well-defined early high-risk period. Moreover, risk factor estimates were highly similar across risk periods and groups. Taken together, our findings question the applicability of early mortality as a standard metric for treatment-associated toxicity.