Situational analysis of the quality of palliative care services across India: a cross-sectional survey.

Objective: Palliative care services in India were established in the 1980s but there is no detailed up-to-date knowledge about the quality-of-service provision nationally. We aim to describe the current quality of palliative care provision in India, as measured against nationally adopted standards. Method: A digital survey adapted from the Indian Association of Palliative Care Standards Audit Tool was administered to 250 palliative care centres. Results: Two hundred and twenty-three (89%) palliative care centres participated - 26.4% were government-run, while the rest include non-governmental organisations, private hospitals, community-led initiatives and hospices. About 200 centres 'often' or 'always' fulfilled 16/21 desirable criteria; however, only 2/15 essential criteria were 'often' or 'always' fulfilled. Only 5.8% provide uninterrupted access to oral morphine. Significance of the results: Palliative care centres in India are falling short of meeting the essential quality standards, indicating the urgent need for new initiatives to drive national change.

To compare the optimal cytoreduction rate in advanced epithelial ovarian cancer stage III/IV after 3 versus 6 cycles of neoadjuvant chemotherapy.

This study aimed to compare the impact of 3 versus 6 cycles of neoadjuvant chemotherapy (NACT) on the optimal cytoreduction in patients of advanced ovarian malignancy during interval debulking surgery (IDS). Thirty patients with advanced-stage IIIc/IV epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer were randomly allocated to receive 6 cycles in the late IDS group versus 3 cycles in early IDS before undergoing interval debulking surgery. A higher percentage of patients achieved optimal cytoreduction in the late IDS group compared to the early IDS group (60 versus 23%) which was statistically significant (p = .010). Giving 6 cycles of NACT before surgery increased the odd of optimal cytoreduction by 10 than giving 3 cycles of NACT which was statistically significant (p = 0.046) Thus, we conclude that administering 6 cycles of neoadjuvant chemotherapy before debulking surgery helps in achieving optimal cytoreduction in a higher number of patients with lesser surgical morbidity.IMPACT STATEMENTWhat is already known on the subject? Currently, there are no established criteria that would help to determine the number of chemotherapy cycles before debulking surgery in patients with advanced ovarian malignancy.What do the results of this study add? Administering 6 cycles of neoadjuvant chemotherapy before debulking surgery helps in achieving optimal cytoreduction in a higher number of patients with lesser surgical morbidity in cases of advanced epithelial ovarian cancer.What are the implications of these findings for clinical practice and/or further research? We conclude that late interval debulking may be used as a treatment option in the advanced stage IIIc/stage IV. However, the findings need to be studied in a larger study group with a longer follow up period.

Chemoradiation therapy induces in vivo changes in gene promoter methylation & gene transcript expression in patients with invasive cervical cancer.

BACKGROUND & OBJECTIVES: Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy. METHODS: In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR. RESULTS: Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P< 0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P< 0.01), DAPK1 and ESR1 (P< 0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P< 0.05) following treatment. INTERPRETATION & CONCLUSIONS: The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response.

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.

Gynecological Cancer as a Second Malignancy in Patients With Breast Cancer.

PURPOSE: The aim of this study was to determine the incidence and risk factors for gynecological cancer as second malignancy (SM) after treatment of breast cancer (BC). METHODS AND MATERIALS: Between January 1985 and December 2007, a total of 2756 patients with BC were analyzed for gynecological cancers as an SM. Analysis was carried out for patient-, disease-, and treatment-related characteristics. The Cox proportional hazards regression model was used to estimate the relative risk of gynecologic malignancies. RESULTS: The median age at BC diagnosis was 49 years and median follow-up of 14 years. In total, 25 cases of gynecological cancer were noted with an incidence of 0.9%. We observed 9 ovarian and endometrium (0.3%) as well as 7 uterine cervix (0.25%) cancers. Family history of BC was the most significant risk factor for SM (relative risk, 7.4; 95% confidence interval, 3.03-18.28; P<0.001). Women with a family history of BC had a higher incidence of endometrial (12%) and ovarian (16%) cancer compared with those who have no family history (0.1%, P = 0.003). Statistically significant higher incidence of endometrial cancer was seen in patients undergoing hormonal therapy (0.4%) as compared with those who are not undergoing hormonal therapy (0.1%, P = 0.001). Most of the endometrial (88.9%) and cervical (71%) cancers were detected at an early stage but ovarian cancers (66.6%) in advanced stage. Chemotherapy and radiotherapy did not increase the risk of gynecological SM. CONCLUSIONS: Women with BC are at risk of developing a second primary gynecological malignancy particularly of endometrium and ovary. Family history of BC was a high risk factor for gynecologic SM. These patients should be followed up for its early detection.

Rhabdomyosarcoma of vulva in a young lady: A rare case report with review of literature.

A 21-year-old lady presented with a rapidly progressive vulvar swelling with inguinal lymphadenopathy for 7 months. Pathological evaluation revealed it as a case of rhabdomyosarcoma. The disease behaved aggressively and she was treated with multimodality treatment.

A case report of peritoneal malignant mesothelioma presenting as primary ovarian mass.

Malignant mesotheliomas are aggressive neoplasms arising from mesothelial cells lining the body cavities. Malignant peritoneal mesothelioma (MPM) account for about one-third of the cases. Though the ovarian involvement may be seen in the background of a diffuse peritoneal involvement, the presentation of MPM as a primary ovarian mass is rare. Here we present such a case who underwent surgery but had residual progressive lesion. She received further chemotherapy resulting in a complete response and is disease free for almost a year.

Cervical embryonal rhabdomyosarcoma and ovarian Sertoli-Leydig cell tumor with congenital absence of unilateral ovary.

We report this first case of synchronous cervical rhabdomyosarcoma and Sertoli-Leydig cell tumor (SLCT) of ovary with congenital absence of unilateral ovary and fallopian tube in a 16-year-old female patient. A review of the English-language literature identified only six cases of double malignancies with cervical rhabdomyosarcoma and SLCT but none of the case was associated with congenital absence of ovary and fallopian tube. When such multiple conditions involving one system occur in an individual, the possibility of single etiology arises, but beside some hypothesis, no definite link could be established in any of the cases reported.

Creation of Minimum Standard Tool for Palliative Care in India and Self-evaluation of Palliative Care Programs Using It.

BACKGROUND: It is important to ensure that minimum standards for palliative care based on available resources are clearly defined and achieved. AIMS: (1) Creation of minimum National Standards for Palliative Care for India. (2) Development of a tool for self-evaluation of palliative care organizations. (3) Evaluation of the tool in India. In 2006, Pallium India assembled a working group at the national level to develop minimum standards. The standards were to be evaluated by palliative care services in the country. MATERIALS AND METHODS: The working group prepared a "standards" document, which had two parts - the first composed of eight "essential" components and the second, 22 "desirable" components. The working group sent the document to 86 hospice and palliative care providers nationwide, requesting them to self-evaluate their palliative care services based on the standards document, on a modified Likert scale. RESULTS: Forty-nine (57%) palliative care organizations responded, and their self-evaluation of services based on the standards tool was analyzed. The majority of the palliative care providers met most of the standards identified as essential by the working group. A variable percentage of organizations had satisfied the desirable components of the standards. CONCLUSIONS: We demonstrated that the "standards tool" could be applied effectively in practice for self-evaluation of quality of palliative care services.

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.

Leiomyosarcoma of the vagina: A rare entity with comprehensive review of the literature.

Primary malignant lesions of the vagina are uncommon, and vaginal sarcomas are even rarer. We describe a rare case of stage I, high-grade leiomyosarcoma of the vagina treated with combined modality treatment. A 39-year-old female presented with vaginal mass and underwent resection. Histopathological examination revealed atypical leiomyoma of the vagina with definite risk of recurrence. Eleven months later, she presented with a recurrent vaginal mass and underwent exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy plus resection of recurrent tumor and partial vaginectomy. The detailed histopathological examination was suggestive of leiomyosarcoma of the vagina. The patient received adjuvant radiotherapy and chemotherapy. The patient is alive and disease-free 29 months postsurgery. Experience with vaginal leiomyosarcomas is limited. The optimal treatment methods have not yet been established because of the rarity of the tumor. We add another case of leiomyosarcoma of the vagina to the limited existing literature.

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.

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.

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.

Dosimetric comparison of vaginal vault ovoid brachytherapy versus intensity-modulated radiation therapy plans in postoperative patients of cervical carcinoma following whole pelvic radiotherapy.

INTRODUCTION: Dosimetric study to compare high dose rate (HDR) vaginal vault ovoid brachytherapy plan versus intensity-modulated radiation therapy (IMRT) boost plan for doses delivered to target volume and organs at risk (OAR) in postoperative patients of cervical carcinoma following whole pelvic radiotherapy (WPRT). MATERIALS AND METHODS: Fifteen postoperative patients of cervical carcinoma suitable for vaginal ovoid brachytherapy following WPRT of 46 Gy/23 fractions/4.5 weeks were included. All were treated with brachytherapy (two sessions of 8.5 Gy each). The equivalent dose for IMRT was calculated by computing biologically effective dose of brachytherapy by linear quadratic model. Dose of brachytherapy (two sessions of 8.5 Gy) was equivalent to IMRT dose of 26 Gy/13 fractions. Doses to target volume and OAR were compared between HDR and IMRT plans. RESULTS: Target volume was well covered with both HDR and IMRT plans, but dose with brachytherapy was much higher (P < 0.05). Mean doses, doses to 0.1, 1, 2, and 5cc, 1/3 (rd) , 1/2, and 2/3 (rd) volume of bladder and rectum were significantly lower with HDR plans. CONCLUSION: In postoperative patients of cervical carcinoma, HDR brachytherapy following WPRT appears to be better than IMRT for tumor coverage and reducing dose to critical organs.

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.

Magnitude and Implications of Interfraction Variations in Organ Doses during High Dose Rate Brachytherapy of Cervix Cancer: A CT Based Planning Study.

Background. Quantifying the interfraction dose variations in the organs at risk (OAR) in HDR intracavitary brachytherapy (HDR ICBT). Methods. Rectum and bladder were contoured in 44 patients of cervical carcinoma on CT after each fraction of HDR ICBT (9 Gy/2 fractions). Interfraction dose variations (VARact) were calculated. Rigid image registration of consecutive fraction images allowed quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. VARhypo was regressed against the VARact to find out to what extent the applicator variation could explain the VARact in the OAR. The rest of the variation was assumed to be due to organ deformation. Results. The VARact in the dose to 2 cc of bladder and rectum were 1.46 and 1.16 Gy, respectively. Increased dose was seen in 16 and 23 patients in the subsequent fraction for bladder and rectum, respectively. Doses to OAR would have exceeded constraints in 16% patients if second fraction was not imaged. VARhypo explained 19% and 47% of the VARact observed for the bladder and rectum respectively. Conclusions. Significant interfraction variations in OAR doses can occur in HDR ICBT. Organ deformations are mostly responsible for this variation.

CT and MR image fusion of tandem and ring applicator using rigid registration in intracavitary brachytherapy planning.

The purpose of this study is to find the uncertainties in the reconstruction of MR compatible ring-tandem intracavitary applicators of high-dose rate image-based brachytherapy treatment planning using rigid registration of 3D MR and CT image fusion. Tandem and ring reconstruction in MR image based brachytherapy planning was done using rigid registration of CT and MR applicator geometries. Verifications of registration for applicator fusion were performed in six verification steps at three different sites of tandem ring applicator set. The first site consists of three errors at the level of ring plane in (1) cranio caudal shift (Cranial Shift) of ring plane along tandem axis, (2) antero-posterior shift (AP Shift) perpendicular to tandem axis on the plane containing the tandem, and (3) lateral shift (Lat Shift) perpendicular to the plane containing the tandem at the level of ring plane. The other two sites are the verifications at the tip of tandem and neck of the ring. The verification at the tip of tandem consists of two errors in (1) antero-posterior shift (AP Shift) perpendicular to tandem axis on the plane containing the tandem, and (2) lateral shift (Lat Shift) perpendicular to the plane containing the tandem. The third site of verification at the neck of the ring is the error due to the rotation of ring about tandem axis. The impact of translational errors from -5 mm to 5 mm in the step of 1 mm along x-, y-, and z-axis and three rotational errors about these axes from -19.1° to 19.1° in the step of 3.28° on dose-volume histogram parameters (D(2cc), D(1cc), D(0.1cc), and D(5cc) of bladder, rectum, and sigmoid, and D90 and D98 of HRCTV were also analyzed. Maximum registration errors along cranio-caudal direction was 2.2 mm (1 case), whereas the errors of 31 out of 34 cases of registration were found within 1.5 mm, and those of two cases were less than 2mm but greater than 1.5 mm. Maximum rotational error of ring about tandem axis was 3.15° (1.1 mm). In other direction and different sites of the ring applicator set, the errors were within 1.5 mm. The impacts of registration errors on DVH parameters of bladder, rectum, and sigmoid were very sensitive to antero-posterior shift. Cranio-caudal errors of registration also largely affected the rectum DVH parameters. Largest change of 17.95% per mm and 20.65% per mm in all the DVH parameters of all OARs and HRCTV were observed for ϕ and Ψ rotational errors as compare to other translational and rotational errors. Catheter reconstruction in MR image using rigid registration of applicator geometries of CT and MR images is a feasible technique for MR image-based intracavitary brachytherapy planning. The applicator regis-tration using the contours of tandem and neck of the ring of CT and MR images decreased the rotational error about tandem axis. Verification of CT MR image fusion using applicator registration which consists of six steps of verification at three different sites in ring applicator set can report all the errors due to translation and rotational shift along θ, ϕ, and Ψ. ϕ and Ψ rotational errors, which produced potential changes in DVH parameters, can be tackled using AP Shift and Lat Shift at the tip of tandem. The maximum shift was still found along the tandem axis in this technique.

Primitive neuroectodermal tumor of the uterine cervix diagnosed during pregnancy: a rare case with review of literature.

Primitive neuroectodermal tumors of the cervix are very rare. A 28-year-old pregnant woman presented with a cervical mass. The tumor was staged as IB2. The biopsy from tumor was suggestive of malignant small round cell tumor. She then underwent termination of pregnancy followed by radical hysterectomy. Based on morphologic and immunohistochemical profile, a diagnosis of peripheral primitive neuroectodermal tumor of the cervix was made. The patient received adjuvant chemotherapy and radiotherapy. The patient is alive and disease-free 33 months post-surgery. The present case highlights the importance of keeping primitive neuroectodermal tumors in the differential diagnosis of small cell neoplasms of the uterine cervix. Pregnancy should not be a barrier to early detection and treatment of this potentially aggressive tumor. The optimal treatment methods have not yet been established because of the rarity of the tumor.