Impact of age on outcomes in young women with breast cancer.

BACKGROUND: In this study, we compared outcomes in young and very young patients with breast cancer (BC). MATERIALS AND METHODS: Between January 1990 to December 2010, 414 young women (age ≤35 years) with BC were registered in the radiotherapy (RT) outpatient department. Patients were divided into young (31-35 years) and very young (18-30 years). They were compared for clinical, pathological characteristics, and treatment-related factors such as RT and systemic therapy. Outcomes compared between the two groups were locoregional recurrence rate (LRR), local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and toxicities. LRFS, DFS, and OS were estimated using the Kaplan-Meier method. RESULTS: Out of 414 patients, 138 and 276 were very young and young, respectively. Clinical, pathological, and treatment characteristics were balanced between the two groups except for more patients in the young group who had pN3 disease and received hormonal therapy; 41 (15%) versus seven (5%) and 171 (62%) versus 62 (45%) in the very young group, respectively. Median follow-up was 84 months (range 12-363 months). LR was seen in 16 (11.6%) and 25 (9%) patients in the very young and young groups, respectively (p = 0.28). The hazard ratios for LR, disease recurrence, and death in the very young group relative to the young group were 1.11 (p = 0.25), 1.0 (p = 1.0), and 1.05 (p = 0.79), respectively. Estimated 10-year LRFS, DFS and OS were 80% versus 86%, 63% versus 61%, and 66% versus 64% in the very young and young groups, respectively. Lymphedema, cardiac toxicity, and second malignancy developed in seven (5%) versus 23 (8%), one (1%) versus three (1%), and seven (5%) versus 18 (7%) patients in the very young and young groups, respectively. CONCLUSION: In very young and young patients with BC, there was no significant difference in LRR, LRFS, DFS, or OS. Toxicities were also comparable between the two groups.

Correlation of oral mucosa dose and volume parameters with Grade 3 mucositis, in patients treated with volumetric modulated arc radiotherapy for oropharyngeal cancer?

BACKGROUND: Oral mucositis is the dose-limiting toxicity of chemoradiation in oropharyngeal cancer patients, which can be minimized by giving constraints to oral mucosa. However, the constraints defined in literature are extrapolated from chemoradiation in head and neck cancers as a whole. This study aims to determine oral mucosa dose-volume parameters that can predict grade ≥ 3 acute oral mucositis in oropharyngeal cancer patients treated with volumetric modulated arc radiotherapy. METHODS: This prospective study was done in 52 patients of locally advanced oropharyngeal cancer treated with Volumetric modulated arc radiotherapy. Dose-volume histogram data were extracted and then acute oral mucosa toxicity was analysed. Receiver operating characteristic analysis and logistic regression were carried out to determine predictive factors for grade ≥ 3 mucositis. RESULTS: Grade ≥ 3 acute oral mucositis occurred in 57.6% (30/52) patients in the study. V30Gy > 53.35% (P = 0.005) was an independent dosimetric factor related to grade ≥ 3 acute toxicity. In the receiver operating characteristic curve, the area under V30Gy was 0.770 (P = 0.001); the cut-off value of V30 was 46.23% (sensitivity, 0.80; specificity, 0.91). CONCLUSIONS: Dose-volume histogram analysis predicts V30 > 53.35% as independent factors for grade ≥ 3 acute oral mucositis in patients with oropharyngeal cancers treated with Volumetric modulated arc radiotherapy. Studies in future with more patient number can further validate the above results.

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India.

Background: Young women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India. Materials and methods: Between January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35-40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method. Results: Of total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1-30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82% (p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups. Conclusion: Young BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease.

Late-term effects of hypofractionated chest wall and regional nodal radiotherapy with two-dimensional technique in patients with breast cancer.

PURPOSE: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. METHODS: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at dmax and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). RESULTS: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. CONCLUSION: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. XXXX).

Fractionated Palliative Pelvic Radiotherapy as an Effective Modality in the Management of Recurrent/Refractory Epithelial Ovarian Cancers: An Institutional Experience.

BACKGROUND: The advent of effective chemotherapeutic agents for ovarian carcinoma has made radical abdomino-pelvic radiation redundant. Nevertheless, palliative pelvic radiotherapy still has a role in palliating local symptoms. However, its effect on progression-free survival (PFS) may be debated. AIMS: To study the outcome of fractionated palliative pelvic radiotherapy in relapsed ovarian cancers in terms of symptom control and PFS. METHODS: Twenty-three patients of ovarian cancers, heavily pretreated with chemotherapy and with recurrent or residual pelvic masses, were planned for palliative pelvic radiotherapy to the dose of 46-50 Gy in 23-25 fractions in 4.5-5 weeks. Symptom control and outcomes have been analyzed. RESULTS: Post-radiotherapy, abdominal pain was controlled in 15 out of 17 patients (88.2 %), bleeding per vaginum in all 5 patients and vaginal discharge stopped in 4 out of 5 patients (80 %). On follow-up, of 23 patients, 17 (74 %) had progressive disease post-radiation, and median time to disease progression was 10 months (range 1-49). On univariate analysis, increased PFS was observed in patients who received radiation late in their course of disease, those with serous histology, and with lesser disease bulk in pelvis (≤2 cm) prior to radiation initiation. CONCLUSION: Fractionated palliative pelvic radiotherapy is an efficient method for symptom palliation in relapsed ovarian cancers. Patients who are heavily pretreated with chemotherapy and have a small-volume pelvic disease may show a prolonged PFS with addition of pelvic radiotherapy. Indications of radiotherapy, however, need to be defined.

Factors Influencing Compliance to Radical Treatment of Middle Thoracic Esophageal Cancer: An Audit from a Regional Cancer Centre.

BACKGROUND: The aim of this study is to identify the factors responsible for interruption of planned treatment in patients of carcinoma mid-thoracic esophagus and also discuss the strategies for improving treatment completion rates. MATERIALS AND METHODS: Patients with nonmetastatic mid-thoracic esophageal cancer who received treatment by multimodality approach using chemotherapy, radiation, and/or surgery were retrospectively analyzed. Factors influencing compliance with planned treatment completion were evaluated, and their significance was determined using multivariate Cox regression analysis. RESULTS: Ninety-one patients were reviewed. Median follow-up period was 11 months. Of 15 patients planned with neoadjuvant chemoradiation followed by surgery (Group 1), only 6 (40%) could complete the treatment. Similarly, only 19 out of 36 patients (52.8%) completed the planned definitive chemoradiation (Group 2). Furthermore, of forty patients planned with definitive radiotherapy (Group 3), 29 patients only (72.5%) completed this schedule. The rate of completion of therapy was worst in Group 1. The most common reason for noncompletion of planned treatment was nutritional inadequacy and excessive weight loss in all groups. In addition, chemotherapy-induced myelosuppression (P = 0.05) was the factor leading to treatment interruption in Group 2 and radiation-induced acute mucositis (P = 0.02) and lost to follow-up (P = 0.02) were the factors in Group 3. CONCLUSIONS: Rate of treatment completion significantly impacts survival rates. Nutritional inadequacy was the most common factor for noncompletion of planned treatment. A well-trained management team consisting of oncologist, dietitian, and psychotherapist can help overcome these factors and thereby improve the treatment completion rates.

Dosimetric correlation of acute and late toxicities in high-risk prostate cancer patients treated with three-dimensional conformal radiotherapy followed by intensity modulated radiotherapy boost.

INTRODUCTION: In prostate cancer, higher radiation doses are often related to higher local control rates. However, the clinical effect of these higher doses on normal tissue toxicities is generally overlooked. We dosimetrically analyze sequential intensity modulated radiotherapy (IMRT) plans in high-risk prostate cancer patients and correlate them with acute and late normal tissue toxicities. MATERIALS AND METHODS: Twenty-five high-risk prostate cancer patients were planned with three-dimensional conformal radiotherapy to a dose of 50 Gy delivered in 25 fractions in 5 weeks, followed by seven-field IMRT boost, to a dose of 24 Gy delivered in 12 fractions in 2.5 weeks, along with hormonal therapy. Acute and late toxicities were analyzed using Radiation Therapy Oncology Group toxicity criteria. Student's t-test was used for correlating doses received by normal tissues with toxicity grade. Five-year disease-free survival (DFS) and biochemical relapse-free survival (RFS) were evaluated using Kaplan-Meier analysis. RESULTS: Median follow-up of patients was 65 months. Of 25 patients, two developed acute Grade 2 rectal toxicity. Only 1 patient developed acute Grade 2 bladder toxicity. Late Grade 2 and 3 rectal toxicity was seen in 2 and 1 patient, respectively. Late Grade 2 and 3 bladder toxicity was seen in 1 patient each. Grade 2 or more acute rectal toxicity correlated significantly with rectal volume receiving >70 Gy (P = 0.04). The 5-year DFS and biochemical RFS was 70.2% and 79.2%, respectively. One patient failed locally and seven failed at distant sites. CONCLUSION: Sequential IMRT with a dose of 74 Gy and maximum androgen blockade is well tolerated in high-risk patients in Indian setup with adequate control rates.

Rare presentation of urachal adenocarcinoma with skip metastasis to colon.

Urachal carcinoma is a rare malignancy constituting <1% of bladder malignancies. The disease arises from a malignant transformation of rests of enteric epithelium in the urachus. Most common sites of metastasis are lung, liver, and bone. We report a postoperative case of urachal carcinoma presenting with distant metastasis to lung and skip lesions in colon. As both urachal and colon carcinoma share common histopathological features, most of the literature suggested using chemotherapy regimens similar to those recommended for colon malignancies. There are no randomized trials till date regarding the management of urachal adenocarcinomas except for the primary treatment being surgery.

Human papillomavirus-associated cancers: A growing global problem.

Human papillomavirus (HPV) infection is linked with several cancers such as cancer cervix, vagina, vulva, head and neck, anal, and penile carcinomas. Although there is a proven association of HPV with these cancers, questions regarding HPV testing, vaccination, and treatment of HPV-related cancers continue to remain unanswered. The present article provides an overview of the HPV-associated cancers.

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.

Leiomyosarcoma of inferior vena cava: Case series of four patients.

Primary vascular leiomyosarcoma (LMS) is a rare tumor accounting for 2% of all LMSs, with the most common site being inferior vena cava (IVC). Overall prognosis is poor, with median survival of 2 years only. We present four cases diagnosed with LMS of IVC, treated with surgery, radiation and chemotherapy. The diagnosis was made based on imaging, intra-operative details and histopathology report and after excluding primary LMS arising from other retroperitoneal structures.

Pelvic nodal CTV from L4-L5 or aortic bifurcation? An audit of the patterns of regional failures in cervical cancer patients treated with pelvic radiotherapy.

OBJECTIVE: To assess the patterns of recurrence in cervical cancer patients treated with pelvic nodal clinical target volume at L4-L5 junction instead of aortic bifurcation. METHODS: Records of patients with locally advanced cervical cancer treated with chemo-radiation were reviewed. Patients treated with standard pelvic fields (superior border of the field at L4/L5 junction), without any radiological evidence of regional lymphadenopathy (<10 mm) were included in the study. The level of aortic bifurcation was retrospectively documented on computed tomography. Patterns of recurrences were correlated to the aortic bifurcation and the superior border of the radiation fields (L4/L5). RESULTS: Aortic bifurcation was above the radiation fields (above L4/5) in 82 of 116 (70.7%) patients. Of the nine patients that recurred above the radiation field, 5 (55%) were above L4/5 failures, i.e. between aortic bifurcation and L4/5, and 4 (45%) had para-aortic failures. On retrospective analysis, 16 patients were found to have subcentimeter lymph nodes and higher nodal failures (7/16) were observed in patients with subcentimeter regional lymph nodes at diagnosis. CONCLUSIONS: Superior border of nodal clinical target volume should ideally include the aortic bifurcation instead of L4-L5 inter space in patients with locally advanced cervical cancer. Radiotherapy fields need to be defined cautiously in patients with subcentimeter pelvic lymph nodes.

Radiotherapy for ovarian cancers - redefining the role.

Radiation therapy in ovarian cancers has been considered an outdated concept for many years, mainly due to toxicity and failure to show benefit in terms of survival. Chemotherapy has been extensively used after surgery for these cancers and it has almost replaced radiation therapy as an adjuvant treatment. Nevertheless, failures in ovarian cancers continue to occur even with the use of newer and effective chemotherapy regimens. About 70% patients demonstrate recurrence in the abdomen or pelvis after first line chemotherapy in ovarian cancers. With advances in technology and sophistication of radiation techniques, along with the molecular and biological knowledge of distinct histological subtypes, there is a need to redefine the role of radiation therapy. This review article focuses on the literature on use of radiation in ovarian cancers and its rationale and indications in the present day. For this, a literature pub med/medline search was performed from January 1975 to March 2014 to redefine the role of radiotherapy in ovarian cancers.

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.

Sarcomatoid variant of urothelial carcinoma of the urinary bladder.

Sarcomatoid carcinoma of the urinary bladder is a rare presentation. Less than 100 case reports have been published in the literature. It has been considered as an aggressive variant of bladder carcinoma. Though different treatment modalities have been tried in the literature, yet radical cystectomy followed by adjuvant chemotherapy and radiation should be preferred in all patients, in view of high incidence of local and distant metastasis.

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.

Conventional four field radiotherapy versus computed tomography-based treatment planning in cancer cervix: A dosimetric study.

BACKGROUND: With advancements in imaging, wide variations in pelvic anatomy have been observed, thus raising doubts about adequate target volume coverage by conventional external radiotherapy fields based on bony landmarks. The present study evaluates the need for integrating computed tomography (CT)-based planning in the treatment of carcinoma cervix. AIMS: To estimate inadequacies in target volume coverage when using conventional planning based on bony landmarks. MATERIALS AND METHODS: The study consisted of 50 patients. Target volume delineation was done on planning CT scans, according to the guidelines given in literature. The volume of target receiving 95% of prescribed dose (V95) was calculated after superimposing a conventional four field box on digitally reconstructed radiograph. The geographic miss with conventional four field box technique was compared with the CT-based target volume delineation. RESULTS: In 48 out of 50 patients, the conventional four field box failed to encompass the target volume. The areas of miss were at the superior and lateral borders of the anterior-posterior fields, and the anterior border of the lateral fields. The median V95 for conventional fields marked with bony landmarks was only 89.4% as compared to 93% for target delineation based on CT contouring. CONCLUSIONS: Our study shows inadequate target volume coverage with conventional four field box technique. We recommend routine use of CT-based planning for treatment with radiotherapy in carcinoma cervix.

Effectiveness of Two High-dose-rate Intraluminal Brachytherapy Schedules for Symptom Palliation in Carcinoma Esophagus: A Tertiary Care Center Experience.

AIM: The aim was to analyze different radiation schedules with high-dose-rate (HDR) brachytherapy in patients with unresectable carcinoma esophagus in terms of dysphagia-free survival (DyFS), local control (LC), disease-free survival (DFS), and complications. MATERIALS AND METHODS: Eighty-six patients were studied under three different radiation schedules: Schedule A - radiation 35 Gy/15# followed by HDR brachytherapy 6 Gy each in two sessions; schedule B - chemoradiation 35 Gy/15# with weekly injection cisplatin 30 mg/m(2) infusion and 5-fluorouracil 325 mg/m(2) bolus followed by HDR brachytherapy 6 Gy each in two sessions; and schedule C - same chemoradiation dose followed by HDR brachytherapy three sessions of 4.68 Gy each. The median follow-up was 12.1 months. RESULTS: Treatment compliance was good. There were no significant differences in the incidence of acute toxicities across the three schedules. No grade III toxicities were noted. At 1 month, 27 patients had dysphagia improvement, which was not different across the three schedules. At 6 months, schedule C showed a trend toward better symptom control of dysphagia (dysphagia free=55%). The 2-year DyFS reached 49.5% in schedule C. Two-year LC rates were approximating 89% in both chemoradiation schedules versus 67.6% in schedule A. The 2-year DFS was also high in chemoradiation schedules. Major complications like ulceration and tracheoesophageal fistulas were more often seen with schedule B with a higher dose per fraction of the brachytherapy schedule. CONCLUSION: In unresectable carcinoma esophagus, radiation-only schedules are associated with lower LC and DFS rates. Concurrent chemoradiation followed by a brachytherapy boost is feasible in suitable patients with a good Karnofsky performance score and are associated with higher DyFS, LC, and DFS with acceptable toxicities. Still there is a need for the standardization of HDR brachytherapy schedules with chemoradiation protocols.