Assessment of Voice Outcomes Post Chemo-Radiotherapy in Non-Laryngeal Head & Neck Cancers Using Electroglottography and Voice Symptom Scale (VoiSS) Questionnaire.

BACKGROUND: Laryngeal toxicity (LT) following concurrent chemo-radiotherapy (CCRT) for non-laryngeal head & neck cancers(NLHNC) has been inadequately studied. Electroglottography (EGG), a non-invasive technique for objective quantification of LT, measures the change in electrical impedance generated by glottic closure. AIM: Objective and subjective assessment of acute LT post-CCRT in NLHNC. MATERIALS AND METHODS: A prospective study on 30 NLHNC patients, treated with CCRT; 66-70Gy/33- 35fractions with weekly Cisplatin. Flexible laryngoscopic examination and EGG were performed at baseline, 6weeks, and 3months post-CCRT; Grades of LT and contact quotients(CQ) were documented. Patientreported outcomes of voice-related quality of life(QoL) performed at the same intervals, using a 30-item Voice Symptom Scale (VoiSS) questionnaire. STATISTICAL ANALYSIS: Results of continuous measurements were studied by mean +/- standard deviation. Analysis of variance (ANOVA) was used for comparison of pretreatment and post-treatment results in more than two groups. Significance was assessed at 5% level ofsignificance. Post- hoc analysis has been done using Tukey-Krammer method for multiple comparisons. Correlation analysis was performed using Pearson correlation test. RESULTS: 26/30 patients completed CCRT; 14 were available at 6weeks; 10 at 3months post-CCRT for analysis. At 6 weeks, 3/14(21.5%) patients had Grade II LT; 11/14(78.57%) had grade III. At 3months, 2/10(20%) had Grade I, 6/10(60%) had grade II but 2/10(20%) had worsened to grade IV. Mean CQ at baseline was 50.77 +/- 5.55; which decreased at 6 weeks to 48.56 +/- 4.66 and further at 3months to 45.56 +/- 4.66 (>0.05) suggestive of glottic hypo-adduction. VoiSS responses showed a significant impact on QoL in all three domains at six weeks and three months post-CCRT, compared to baseline (P < 0.0001). CONCLUSION: Electroglottography is a potential tool to quantify acute LT post CCRT. Patient-reported outcomes may not correlate to the objective measures of laryngeal toxicity and require separate recording and reporting. A larger sample size would be required to draw further significant correlations. Key Words: Electroglottography; laryngeal toxicity; head neck cancer; voice; chemo-radiotherapy.

Estimation of dose-volume parameters of female urethra as organ-at-risk during interstitial brachytherapy in gynecological malignancies.

PURPOSE: Interstitial brachytherapy (ISBT) is often used as post-external beam radiotherapy (EBRT) to treat locally advanced gynecological malignancies. Female urethra is in close proximity to the target during ISBT. However, it has not been evaluated as an organ-at-risk (OAR). Overlapping symptoms caused by radiation-induced bladder toxicity vs. urethral toxicity make it difficult to identify and report urethral toxicities separately. This was a retrospective study to estimate dose-volume parameters of female urethra during high-dose-rate ISBT. MATERIAL AND METHODS: Data of 24 patients with gynecological malignancies treated by ISBT were selected. Urethra and periurethral regions were retrospectively contoured. Mean volume, Dmax, Dmean, D2cc, D1cc, D0.5cc, D0.2cc, and D0.1cc were documented. Unpaired t-test was used for comparison of means. RESULTS: 20/24 Ca. cervix, 1/24 Ca. vagina, and 3/24 Ca. vaginal vault received 6-6.5 Gy in 4 ISBT fractions. Mean urethral length was 3.54 ±0.55 cm. Mean doses received by urethra per BT fraction were Dmax = 4.23 ±1.32 Gy, Dmean = 2.71 ±1.01 Gy, D0.2cc = 3.31 ±1.07, and D0.1cc = 3.54 ±1.09 Gy. Comparison of total BT 2 Gy equivalent dose (EQD2) with 4 fractions for urethra between patients with (9/24) and without anterior vaginal wall (15/24) involvement included Dmean = 18.79 ±7.49 Gy vs. 11.14 ±6.15 Gy*, D1cc = 10.90 ±10.03 Gy vs. 4.54 ±3.93 Gy*, D0.5cc = 19.50 ±8.69 Gy vs. 11.97 ±6.54 Gy*, D0.2cc = 23.78 ±8.94 Gy vs. 15.51 ±7.39 Gy*, and D0.1cc = 25.88 ±9.37 Gy vs. 17.39 ±8.03 Gy*, respectively (*p < 0.05). CONCLUSIONS: Female urethra receives significant doses during ISBT for gynecological malignancies, especially when the anterior vaginal wall is within the target volume. Reporting doses to urethra would enable to develop clinical correlation and dose-volume constraints for urethra as organ-at-risk in future.

Does Radiation Dose to Gastric Fundus during Neoadjuvant Chemoradiotherapy for Esophageal Carcinoma Have an Impact on Postoperative Anastomotic Leak?

BACKGROUND: Radiation dose received by the gastric fundus (GF) in neoadjuvant chemoradiotherapy (NACRT) may influence the development of postoperative anastomotic leak (AL) in the management of resectable esophageal carcinoma (EC) by trimodality therapy. The present study aims to evaluate dose-volume parameters of the GF and their association with occurrence of AL in EC. MATERIALS AND METHODS: A retrospective analysis was performed of 27 patients with EC who underwent NACRT followed by esophagectomy with cervical esophagogastric anastomosis between January 2015 and July 2018. The GF was retrospectively contoured; dose-volume parameters of the GF were recorded. Postoperative AL was identified from surgical records. Logistic regression analysis was used to identify risk factors associated with AL. RESULTS: The mean age of the patients was 51 ± 10.5 years; 56% (15/27) had involvement of lower 1/3 esophagus, 10/27 (37%) midthoracic esophagus, and 2/27 (7%) upper thoracic esophagus; 40% (11/27) patients developed postoperative AL and 7/11 had distal and 4/11 had mid thoracic esophageal lesions. Four of five (80%) patients treated by 3-dimensional conformal radiotherapy versus 7/22 (32%) patients treated by volumetric modulated arc therapy developed AL (p = 0.12). Univariate logistic regression revealed no significant correlation between Dmean, Dmax, V20, V25, V30, V35, D50, and AL. 8/27 patients underwent ischemic preconditioning of gastric conduit, and 2/8 had AL; 19/27 did not undergo preconditioning, and 9/19 patients experienced AL (p = 0.4). CONCLUSION: There was no significant negative impact of the dose received by the GF in NACRT upon AL rates. Further studies with a larger sample size are required to clarify this issue.

Malignant melanoma of urethra in a young female - Case report and Literature review.

Malignant mucosal melanoma (MM) is a rare and aggressive neoplasm, which behaves differently from its cutaneous counterpart. MM of head and neck account for 55.4%, genital tracts - 18%, ano-rectal - 23.8% and urinary tract - 2.8%. Less than 200 cases of urethral melanomas have been reported in literature, out of which MM of female urethra represent only 0.2% of primary melanomas. Owing to the delayed presentation, early onset of metastasis and aggressive tumor biology, prognosis has remained largely poor despite adequate local control in MM. Surgery is the mainstay of management, with adjuvant radiation contributing to local control but not overall survival benefit. Chemotherapy and immunotherapy options are being explored in both adjuvant and palliative setting. We hereby, report the clinical presentation, management, and course of a rare case of urethral melanoma in a young female patient. After ruling out metastatic disease at presentation, local control was achieved by wide local excision with distal urethrectomy and modified Singapore flap reconstruction along with bilateral modified superficial inguinal block dissection; followed by adjuvant radiotherapy in view of close margins. However, she developed distal recurrence three months post adjuvant therapy, thus reflecting the aggressive biology of this class of rare tumor.

Evaluation of dosimetric impact of inter-application and intra-application variations in fractionated high-dose-rate intra-cavitary brachytherapy of cervical cancer.

PURPOSE: To evaluate feasibility and safety of execution of optimized intra-cavitary brachytherapy (ICBT) plan of first fraction in subsequent fractions in high-volume, low-resource centers. MATERIAL AND METHODS: This non-randomized prospective study included 30 cervical cancer patients, who underwent 4 fractions of high-dose-rate (HDR)-ICBT in 2 applications, one week apart, 2 fractions per application delivered on two consecutive days. Computed tomography (CT) simulation was done before each fraction, organs at risk (OARs) were contoured on all sets of CT images. Optimized plans were generated for each set of CT images and executed for the treatment. Test treatment plans were retrospectively generated by applying first treatment fraction's dwell times adjusted for decay, and dwell positions of the applicator for subsequent treatment fractions paired t-test was performed to analyze D2cc dose variations of OARs among the paired sets of plans. RESULTS: Comparison between the plans showed daily plans provided lower D2cc to OARs than test plans. In intra-application plan comparison, there was a significant dose reduction to 2 cc sigmoid (p = 0.021) and bladder (p = 0.007) in daily plan. Mean D2cc of optimized and unoptimized plans were 361.35 ±114.01 and 411.70 ±152.73 for sigmoid, and 511.23 ±85.47 cGy and 553.57 ±111.23 cGy for bladder, respectively. In inter-application, D2cc rectum and sigmoid demonstrated a statistically significant dose variation (p = 0.002) and (p = 0.007), with mean D2cc rectum of optimized and unoptimized plans being 401.06 ±83.53 cGy and 452.46 ±123.97 cGy, and of 2 cc sigmoid 340.84 ±117.90 cGy and 387.79 ±141.36 cGy, respectively. CONCLUSIONS: Fractionated HDR brachytherapy amounts to significant variation in OAR doses if re-simulation and re-plan is not performed for every fraction and ICBT application. Therefore, plan of the day with optimization of the doses to target and OARs must be followed for each fraction.

Dosimetric comparison of manual forward planning with uniform dwell times versus volume-based inverse planning in interstitial brachytherapy of cervical malignancies.

AIM: Dosimetic comparison of manual forward planning(MFP) with inverse planning(IP) for interstitial brachytherapy(ISBT) in cervical carcinoma. BACKGROUND: Brachytherapy planning by MFP is more reliable but time-consuming method, whereas IP has been explored more often for its ease and rapidness. The superiority of either is yet to be established. METHODOLOGY: Two plans were created on data sets of 24 patients of cervical carcinoma who had undergone ISBT, one by MFP with uniform dwell times and another IP on BrachyVision 13.7 planning system with a dose prescription of 600 cGy. Isodose shaper was used for improving conformity & homogeneity. Dosimetric parameters for target and organs at risk (OARs) were recorded. Conformity index (COIN), dose homogeneity index (DHI), overdose index (OI), Coverage index (CI) and dose nonuniformity ratio (DNR) were calculated. RESULTS: Mean high risk clinical target volume: 73.05(±20.7)cc, D90: 5.51 Gy vs. 5.6 Gy (p = 0.017), V100: 81.77 % vs. 83.74 % (p = 0.002), V150: 21.7 % vs. 24.93 % (p = 0.002), V200: 6.3 % vs. 6.4 % (p=0.75) for IP and MFP, respectively. CI: 0.81(IP) and 0.83(MFP) (p = 0.003); however, COIN was 0.79 for both plans. D2cc of OARs was statistically better with IP (bladder 54.7 % vs. 56.1 %, p = 0.03; rectum 63 % vs. 64.7 %, (p = 0.0008). CONCLUSION: Both MFP and IP are equally acceptable dosimetrically. With higher dose achieved to the target, for a similar OAR dose, MFP provides greater user flexibility of dwell positions within the target as well as better optimization. Isodose shaper may be carefully used for fine tuning. Larger sample sizes and clinical correlation will better answer the superiority of one over the other.

Gastric Adenocarcinoma in a 16-Year-Old Female.

BACKGROUND: Primary gastric adenocarcinoma commonly occurs in the elderly in the sixth to seventh decade of life but is exceedingly rare in children and adolescents, accounting for only 0.05% of pediatric gastrointestinal malignancies. Because of the nonspecific clinical presentation, gastric adenocarcinomas in children and adolescents are often metastatic when they are discovered. CASE REPORT: We describe a case of gastric adenocarcinoma in a 16-year-old female who was diagnosed early and successfully treated with surgery and chemoradiation by volumetric modulated arc technique. CONCLUSION: The possibility of gastric adenocarcinoma should be considered in children and adolescents with persistent nonspecific symptoms of vomiting and upper abdominal pain so that the diagnosis can be made at early stages and radical treatment can be offered.

Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) used for definitive management of locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ preservation at the cost of preservation of function. Vocal cords, being within the field of irradiation, undergo acute and chronic changes which adversely impacts the patients' voice. AIMS: To assess the acute changes in the acoustic characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC. MATERIALS AND METHODS: Thirty patients with HNSCC treated with CCRT, a total dose of 66-70 Gy/33-35 fractions at five fractions/week, with weekly cisplatin. Acoustic analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3 months post-CCRT. Statistical analysis of the parameters using ANOVA and Student's t-test was performed. RESULTS: Of the thirty patients, 26 patients completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%]) developed Grade III toxicity. On AA, both increase and decrease in mean F0 from baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14 available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for both genders; jitter and shimmer, and NHR values maintained an increase (P > 0.05). CONCLUSIONS: Periodic AA allows quantification of voice changes and mapping of vocal toxicity induced by CCRT.