A Systematic Review of Radiation-Related Lymphopenia in Genito-urinary Malignancies.

BACKGROUND: The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. METHODOLOGY: To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. RESULTS: Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. CONCLUSION: One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.

Risk and impact of radiation related lymphopenia in lung cancer: A systematic review and meta-analysis.

BACKGROUND: Despite the modern advances in treatment techniques, the survival of locally advanced lung cancer patients continues to remain poor. Circulating lymphocytes have an important role to play in local immune response to RT as well as immune checkpoint inhibitors, and radiation related lymphopenia has been associated with inferior survival in various tumors. METHODS: We undertook this systematic review and meta-analysis to evaluate the literature on risk and impact of lymphopenia in thoracic tumors. A systematic methodology search of the PubMed, Embase and Cochrane library was performed and eligible studies selected based on pre-defined inclusion and exclusion criteria. Review Manager Version 5.4.1 was used for the meta-analysis. RESULTS: Fourteen studies were included in the final systematic review and 10 in the quantitative analysis. Overall mean incidence of severe lymphopenia (absolute lymphocyte count < 500) was 64.24%. The patients with severe lymphopenia were at increased risk of death with a pooled HR of 1.59 (95% CI: 1.40, 1.81, I2 = 17%, P < 0.001) and progression with a pooled HR of 2.1 (95% CI: 1.57, 2.81, I2 = 59%, P < 0.001) compared to patients with no severe lymphopenia. Dosimetric parameters including gross tumor volume, lung V5 and heart V5 were predictive of lymphopenia, while advanced age, lower baseline lymphocyte counts, higher stage and large tumor size were other risk factors. Models predicting estimated radiation dose to lymphocytes were a good surrogate for treatment outcomes. CONCLUSION: Radiation related lymphopenia is associated with increased hazard of progression and death in lung cancer. Minimizing the lung and heart dose, especially in patients with concurrent other risk factors can reduce lymphopenia and potentially improve treatment outcomes in these patients.

Flattening filter free VMAT for a stereotactic, single-dose of 30 Gy to lung lesion in a 15-min treatment slot.

Cone-beam CT-guided single dose of lung stereotactic body radiotherapy (SBRT) treatment with a flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a safe and highly effective treatment modality for selective small lung lesions. Four-dimensional (4D) CT-based treatment plans were generated using advanced AcurosXB algorithm for heterogeneity corrections. 6X-FFF beam produced highly conformal radiosurgical dose distribution to the target and reduced lung SBRT fraction duration to less than 10 min for a single dose of 30 Gy, significantly improving patient comfort and clinic workflow. Early follow-up CT imaging results (mean, 8 months) show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow-up in a larger patient cohort managed in this fashion is underway to further validate this treatment approach.

Outcomes in surgically resectable oropharynx cancer treated with transoral robotic surgery versus definitive chemoradiation.

PURPOSE: Optimal treatment strategies for the management of oropharyngeal squamous cell carcinoma (OPSCC) remain unclear. The objective of this study is to examine the role of transoral robotic surgery (TORS) on functional and treatment outcomes. MATERIALS AND METHODS: A retrospective review of patients with OPSCC (tonsil/base of tongue) who underwent TORS with neck dissection± adjuvant therapy between January 2011 to December 2016 were compared to a stage matched cohort of patients treated with primary chemoradiation. Demographic, treatment, and outcome data were collected. RESULTS: 54 patients received primary chemoradiation and 65 patients (surgical group) received TORS ± adjuvant therapy for clinically staged disease meeting study criteria. 25% (N = 17) were treated with surgery alone. The remainder of the surgical group received postoperative radiation (N = 48), half of which received adjuvant chemotherapy (N = 24) in addition to radiation. 63% (N = 41) of the patients did not have risk factors for chemotherapy. No differences in overall or disease free survival were observed with TORS compared to chemoradiation (p = 0.9), although Charlson Comorbidity Index (CCI) was higher in the surgical group (p = 0.01). The strongest predictor of prolonged gastrostomy tube use was not treatment, but rather co-morbidity (p = 0.03), with no significant differences beyond 12 months. CONCLUSION: Although no significant survival differences were observed across treatment groups, this was maintained despite increased comorbidity index in the surgical patients. Given the ability to de-escalate and/or eliminate adjuvant therapy, particularly in a less healthy population, TORS would appear to be the viable treatment option it has become.

Clinical outcomes with MRI-guided image-based brachytherapy in cervical cancer: An institutional experience.

PURPOSE: To evaluate the long-term disease control and toxicity to the organs at risk after dose-escalated image-based adaptive brachytherapy (BT) in cervical cancer. METHODS AND MATERIALS: Sixty patients of cervical cancer were treated with external radiotherapy 46 Gy in 23 fractions with weekly cisplatin and MRI-guided BT 7 Gy × 4 fractions with a minimum dose of 85.7 Gy (EQD2) to the high-risk clinical target volume (HRCTV). The BT dose was initially prescribed to point A and plans were optimized to ensure coverage of both point A and HRCTV while maintaining doses to the organs at risk within the recommended constraints. Patients were followed up clinically every three months for the first two years and six months thereafter. Toxicity scoring for urinary and bowel symptoms was done using CTCAE version 3.0. RESULTS: The mean doses to the point A and D90 HRCTV were 85.5 (±2.75) Gy and 98.4 (±9.6) Gy EQD2 respectively. The mean 2 cc EQD2, the bladder, rectum, and sigmoid were 90.6 Gy, 70.2 Gy, and 74.2 Gy respectively. The overall survival at a median followup of 49.8 months was 91.66%. Six (10%) patients developed grade 3 gastrointestinal toxicity. One patient developed grade 3 bladder toxicity. The incidence of bladder, rectal, and sigmoid toxicity increased significantly with doses >85 Gy, 66 Gy, and >71 Gy EQD2 respectively. CONCLUSIONS: While the incidence of grade 3-4 toxicity was low (8.3% for gastrointestinal toxicity and 1.6% for bladder), the threshold for development of grade 1-2 bladder and rectal toxicity was lower than the doses recommended by the GEC-ESTRO group. By adhering to volume-based prescriptions, there is scope of further reduction in toxicity to organs at risk.

High-dose-rate interstitial brachytherapy in early stage oral tongue cancer - 15 year experience from a tertiary care institute.

PURPOSE: To determine outcomes of interstitial high-dose-rate brachytherapy (HDR-BT) in patients with early stage oral tongue cancer. MATERIAL AND METHODS: Ninety-two patients with stage I and II oral tongue cancer were treated with HDR-BT between 1999 and 2014: brachytherapy alone = 62 (67.4%), and combination of external beam radiotherapy (EBRT) and brachytherapy = 30 (32.6%). Median follow-up was 53.5 months. Patterns of failure, overall survival (OS), disease-free survival (DFS), local control rates (LCR), and nodal control rates (NCR) were determined. RESULTS: 5-year OS, DFS, LCR, and NCR were 73.2%, 58.2%, 64.2%, and 83.8%, respectively. In total, 43 patients (46.7%) failed treatment: isolated local failures = 28 (30.4%), isolated nodal failures = 8 (8.7%), both local and regional failures = 7 (7.6%). While in T1 stage, 5 year LCR were significantly higher in brachytherapy alone group compared to combined EBRT and brachytherapy group (81.7% vs. 62.5%, p = 0.04), the isolated nodal failure rates were not significantly different among the two groups. For T2 stage, NCR were higher in combined EBRT and brachytherapy group compared to brachytherapy alone (92.9% vs. 74.3%). Acute mucositis (grade ≥ 2) was seen more in brachytherapy alone group compared to the combined modality group (87% vs. 66%), and this correlated significantly with the higher biological equivalent dose (BED) in the brachytherapy alone group. CONCLUSIONS: Our study recommends treating patients with brachytherapy alone in T1 stage, and demonstrates the need for addressing nodal region either by neck dissection or nodal irradiation in T2 stage patients. Also, the study highlights the need for dose escalation (from the doses used in the study) in both T1 and T2 stage tumors when using interstitial brachytherapy either as sole modality or as a boost.

Evaluation of intrafraction motion of the organs at risk in image-based brachytherapy of cervical cancer.

PURPOSE/INTRODUCTION: To assess the variation in the doses received by the organs at risk (OARs) that can occur during treatment planning of cervical cancer by image-based brachytherapy. METHODS AND MATERIALS: After intracavitary application, two sets of images-CT and MRI-were obtained. The two sets of images were fused together with respect to the applicator. Contouring was done separately on CT and MR images. Dose received by the OARs on CT images with respect to the plans made on the MR images was estimated and compared with those on the MR images. RESULTS: Although there was always a difference between the dose received by the OARs based on the CT and MRI contours, it was not significant for the bladder and rectum; 2 cc doses differed by 0.49 Gy (±0.44) p = 0.28 for the bladder and 0.30 Gy (±0.29) p = 0.16 for the rectum. The 1 cc and 0.1 cc differences were also not significant. However for the sigmoid colon, there was significant intrafraction variation in the 2 cc doses 0.61 (±0.6) p = 0.001, 1 cc doses 0.73 (±0.67) Gy p = 0.00, and 0.1 cc dose 0.97 (±0.93) Gy p = 0.009. CONCLUSIONS: The variation in the doses to the OARs must be considered while weighing target coverage against overdose to the OARs. Although not significant for the bladder and rectum, it was significant for the sigmoid colon. Estimated doses to OARs on the planning system may not be the same dose delivered at the time of treatment.

Vaginal dose, toxicity and sexual outcomes in patients of cervical cancer undergoing image based brachytherapy.

BACKGROUND: The aim of the study was to evaluate the vaginal dose and toxicity in patients of cervical cancer treated with image guided brachytherapy at our institute. MATERIALS AND METHODS: Thirty-five patients treated with image based brachytherapy for cervical cancer were included. Vaginal contouring was done on MRI at brachytherapy and with CT scans of subsequent brachytherapy fractions. Dose volume parameters (DVH) were reported in accordance with the GEC-ESTRO guidelines. These were correlated with vaginal toxicity (assessed by CTCAE version 3) and quality of sexual life assessed at one year of completion of treatment. RESULTS: Vaginal shortness was observed in 22 out of 30 (62.8%) patients, Nine (25.7%) had vaginal dryness and in 10 (28.5%) patients, there was contact bleeding. No association could be demonstrated between the dose volume parameters and vaginal toxicity in the present study. CONCLUSIONS: The lack of association between dose volume parameters of vagina with vaginal morbidity may be due to uncertainties involved in the delineation of vaginal wall and dosimetry. Future research is required to accurately define vaginal dose distribution to study its correlation with vaginal morbidity. Vaginal morbidity needs to be documented in order to improve the sexual outcome in these patients.

Gonadotrophin releasing hormone analogues for ovarian function preservation in young females undergoing chemotherapy.

Chemotherapy has significantly improved the prognosis of cancer patients with various malignancies. However, female patients, especially those whoich are premenopausal, suffer from significant chemotherapy induced ovarian function impairment, which decreases their quality of life. Many new techniques for ovarian preservation have been established in recent years. Although the use of gonadotrophin releasing hormone analogues (GnRHa) for this purpose is not a new concept, its effectiveness in protection of ovarian function is still debatable. This article deals with studies and metaanalyses which have been undertaken in the past, demonstrating the impact of GnRHa in ovarian function preservation, and whether their use can be implemented in routine practice.

Literature review with PGI guidelines for delineation of clinical target volume for intact carcinoma cervix.

For definitive treatment of carcinoma cervix with conformal radiation techniques, accurate target delineation is vitally important, yet a consensus definition of clinical target volume (CTV) remains variable within the literature. The aim of the present article is to review the guidelines for CTV delineation published in the literature and to present the guidelines practiced at our institute. For this a literature pub med/medline search was performed from January 2000 to December 2012 and reviewed to identify published articles on guidelines for CTV primary and pelvic lymph node (LN) delineation for carcinoma cervix. Taking into consideration the traditional bony landmark based fields for treating cancer cervix, the knowledge of the patterns of disease spread and recurrence and the findings from imaging studies identifying typical anatomic distributions of areas at risk of harbouring subclinical disease, the differences in various guidelines have been analyzed and discussed. The CTV in cervical cancer consists of the CTV nodal and CTV primary. In all the published guidelines, CTV nodal consists of common iliac, external iliac, internal iliac, pre-sacral and obturator group of lymph nodes, and CTV primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, upper third of vagina and uterosacral ligaments. The various guidelines differ however, in the definition for these individual component structures. This is the first report to provide the complete set of guidelines for delineating both the CTV primary and CTV nodal in combination.