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.

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.

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.

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.

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.

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.

Uterine sarcoma-current management and experience from a regional cancer centre in North India.

PURPOSE: We intended to assess the clinicopathological features and treatment outcome in patients of uterine sarcoma. METHOD: A retrospective review of medical records of patients of uterine sarcoma (2002-2007) was conducted. Overall survival (OS) was analyzed by Kaplan-Meier method. RESULTS: Forty-two patients met the study criterion [15 carcinosarcoma, 12 endometrial stromal sarcoma, 11 leiomyosarcoma, 3 undifferentiated endometrial sarcoma (UES), and 1 mixed sarcoma]. Median age and performance status were 52 years and ECOG 0, respectively. All patients underwent primary surgery out of which 66.7 % was total abdominal hysterectomy and bilateral salpingo-oophorectomy. FIGO (2009) stage was I, II, III, IV and unknown in 66.7, 7.1, 14.3, 9.5, and 2.4 % of the patients. Eight patients were kept on follow-up only. Adjuvant radiation, chemoradiation, and chemotherapy were offered in 8, 9, and 3 patients, respectively. Pelvic radiation: 46 Gray/23 fractions/4.5 weeks and vincristine, adriamycin, cyclophosphamide (VAC) regimen were most commonly used. Overall clinical complete response (CR), stable disease (SD), and progressive disease (PD) were, respectively, 59.5, 2.4, and 26.2 % (response not evaluable in 12 %). In the evaluable patients (N = 33), median OS was noted to be 7.67 months (mean 30.19 months). 1- and 2-year actuarial survival were 45.45 and 36.36 %. Stratified by histology, median survival in patients with carcinosarcoma, endometrial stromal sarcoma, leiomyosarcoma, and UES were, respectively, 6.57, 18.7, 6.8, and 9.38 months. On univariate analysis, response to therapy (p = 0.0003), disease stage (p = 0.00001), tumor size (p = 0.02), and performance status (p = 0.03) were significant predictors of OS. Disease stage (p = 0.005) and response to therapy (p = 0.01) retained significance on multivariate analysis. CONCLUSIONS: Median OS of only 6.57, 6.8, and 9.38 months, respectively, in patients with carcinosarcoma, leiomyosarcoma, and UES in our series reflect the aggressive clinical course and poor prognosis of these rare neoplasms, which mandate intensive multimodality therapy. Even in low-grade endometrial stromal sarcoma, median survival of 18.7 months in our series is far from satisfying. However, small series, poor treatment compliance and socio-economic constraints in the Indian scenario are limiting factors in the result analysis.

Differential expression of Fas family members and Bcl-2 family members in benign versus malignant epithelial ovarian cancer (EOC) in North Indian population.

Epithelial ovarian cancer (EOC) represents the most challenging of gynecological malignancies. Defective apoptosis is a major causative factor in the development and progression of cancer. The two important pathways of apoptosis are extrinsic death receptor pathway (Fas family) and intrinsic mitochondrial pathway (Bcl-2 family). In this study, differential protein expression of the major Fas family members (Fas, FasL, and FAP-1) and Bcl-2 family members (Bax, Bcl-2, and Bcl-X(L)) in benign versus malignant surface epithelial ovarian tumors was evaluated at the protein level by immunohistochemistry. The expression of these molecules was compared in 30 benign versus 35 malignant surface epithelial ovarian tumors. The findings of the present study showed that there was no significant difference in the expression of the Fas family members in benign and malignant ovarian tumors. However, benign tumors showed higher levels of anti-apoptotic Bcl-2 protein levels (p < 0.009), whereas malignant tumors showed higher levels of pro-apoptotic Bax (p < 0.001). In general, there was no significant difference in Bcl-X(L) protein levels. The observations made in the present study suggest that alterations in expression of the Fas family and the Bcl-2 family members occur and play a key role in the deregulated growth of epithelial ovarian cancer.

CT or MRI for image-based brachytherapy in cervical cancer.

OBJECTIVE: To compare volumes and doses of tumour and organs at risk with computed tomography vs. magnetic resonance imaging in cervical cancer brachytherapy. METHODS: Seventeen previously untreated patients with cervical cancer suitable for radical treatment were included. All patients underwent brachytherapy using a magnetic resonance imaging-compatible applicator followed by both computed tomography and magnetic resonance imaging. The tumour and organs at risk (bladder, rectum, sigmoid and intestines) were contoured on computed tomography using only clinical findings and on magnetic resonance imaging using GEC-ESTRO guidelines. The volume and doses for tumour and organs at risk were evaluated using two-sided t-test. RESULTS: When magnetic resonance imaging information is not included in contouring on computed tomography images, there is significant underestimation of tumour height and overestimation of the width (P< 0.05). However, there was no significant difference in V(100), D(90) and D(100) for high- and intermediate-risk clinical target volume in computed tomography and magnetic resonance imaging. The volumes and doses to 0.1, 1 and 2 cc for organs at risk were also similar. CONCLUSIONS: Magnetic resonance imaging remains the gold standard for tumour delineation, but computed tomography with clinical information can give comparable results, which need to be studied further. Computed tomography-based contouring can be used comfortably for delineation of organs at risk.

Sarcomas of uterine cervix: clinicopathological features, treatment, and outcome.

OBJECTIVE: Sarcomas constitute less than 1% of all cervical malignancies. The objective of this study was to determine the presentation, pathological findings, treatment, and outcome of patients with cervical sarcoma. METHODS AND MATERIALS: A retrospective analysis of 8 cases of cervical sarcoma diagnosed over a 4-year period from 2006 to 2009 was carried out. The medical records of all patients were reviewed. All pathologic specimens were reviewed by a single pathologist. RESULTS: Of 1804 patients with cervical malignancies, 8 cervical sarcomas were identified. All patients presented with vaginal bleeding and discharge. The lesions were clinically staged as IB2 (3), II B (1) and IIIB (4). Three patients had leiomyosarcoma, 4 patients had a diagnosis of undifferentiated endocervical sarcoma, and one had embryonal rhabdomyosarcoma. Of the 8 patients, 3 absconded after diagnosis. Primary surgery was done in 3 patients of which 2 patients received adjuvant radiotherapy and chemotherapy and one patient absconded after surgery. Primary radiotherapy was given in 2 patients. Three of 8 patients treated with combined modality treatment remain alive and disease free at the last follow-up. CONCLUSIONS: Cervical sarcomas are rare neoplasms and represent a spectrum on histopathology. Most patients present with vaginal bleeding and a bulky cervical mass at the time of diagnosis. The optimal management of these tumors is uncertain owing to its rarity; however, combined modality treatment can result in prolonged survival and cure.

Pediatric astroblastoma: a rare case with a review of the literature.

Astroblastoma is a rare glial tumor with uncertain histopathological origin and unpredictable clinical behavior. We present a case of an 11-year-old girl who presented with headache and blurring of vision for 2 months. A well-demarcated mass was found in the right frontoparietal lobe on a brain MRI. The patient was treated with total tumor resection followed by postoperative radiotherapy. Histologically, the features were suggestive of high-grade astroblastoma. The patient is alive and disease free 23 months after surgery. The characteristic radiological and histopathological features and treatment of this case are described with a literature review.

Palliative care in India: current progress and future needs.

Despite its limited coverage, palliative care has been present in India for about 20 years. Obstacles in the growth of palliative care in India are too many and not only include factors like population density, poverty, geographical diversity, restrictive policies regarding opioid prescription, workforce development at base level, but also limited national palliative care policy and lack of institutional interest in palliative care. Nonetheless we have reasons to be proud in that we have overcome several hurdles and last two decades have seen palpable changes in the mindset of health care providers and policy makers with respect to need of palliative care in India. Systematic and continuous education for medical staff is mandatory, and a major break-through for achieving this purpose would be to increase the number of courses and faculties in palliative medicine at most universities.

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.

Primary gliosarcoma--clinical experience from a regional cancer centre in north India.

AIMS: We intended to assess the clinicopathological features and treatment outcome in patients of primary gliosarcoma, a rare malignant brain tumour. MATERIALS AND METHODS: Medical records were reviewed and data collected on primary gliosarcoma over an 8-year period (2002-2009) from the departmental archives. Overall survival (OS) was analysed by Kaplan-Meier method. RESULTS: Seventeen patients met the study criterion (male:female = 9:8). Median age and performance status at presentation were 50 years and Karnofsky performance scale (KPS) 70, respectively. Symptoms of raised intracranial tension (in 100%) and motor impairment (in 64.7%) were commonly observed. Tumour location was frontal in four patients, temporal in three, parietal in three, thalamic in one, multilobed in five and multicentric in one. All patients underwent maximal safe surgery (total excision-10, near-total excision-2, subtotal excision and decompression-5). On histopathology, all tumours showed biphasic pattern, glial component positive for glial fibrillary acidic protein (GFAP) and mesenchymal component positive for vimentin and reticulin. Atypia, mitoses, necrosis and endothelial proliferation were identified in the glial component. Post-operative radiotherapy (median dose--60 Gy/30#/6 weeks) was used in 15 patients (88.2%). Concurrent and adjuvant chemotherapy with temozolomide (TMZ) were used in two patients depending upon affordability. After the completion of treatment, 35.3% patients were asymptomatic, 23.5% had symptomatic improvement, while 41.2% deteriorated. Salvage therapy for local recurrence was used in three patients (temporal lobectomy-1; total excision-1; TMZ+bevacizumab-1). At last follow-up (FU), eight patients were alive, seven patients dead and two patients lost to FU with symptom. Median overall survival in the evaluable patients (N = 15) was noted to be 8.27 months (6 month survival 60.76%). CONCLUSIONS: Primary gliosarcoma, a variant of glioblastoma poses clinical challenge because of rarity, poor prognosis and limited experience. In our centre, principle of therapy is akin to that of glioblastoma--surgery followed by radiation along with concurrent and adjuvant TMZ. However, chemotherapy is often cost-prohibitive in our setting as mirrored by limited use (17.6%). Median survival of only 8.27 months in our series is in concert with the existing survival result of primary gliosarcoma in world literature (6.25-11.5 months).

Expression of the major fas family and Bcl-2 family of proteins in epithelial ovarian cancer (EOC) and their correlation to chemotherapeutic response and outcome.

Platinum-based chemotherapeutic drugs trigger apoptosis, and deregulation of apoptotic pathways may contribute to chemoresistance. We investigated the role of major Fas and Bcl-2 family members as predictors of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). The expression of Fas, FasL, FAP-1, Bax, Bcl-2, and Bcl-X(L) was analyzed in 35 women with EOC at the transcript level by semiquantitative RT-PCR and at the protein level by immunohistochemistry. The apoptotic index was determined by TUNEL assay. The response to chemotherapy was documented and at the end of six cycles of chemotherapy. Based on their response, two groups were identified: primary chemosensitive (n = 20) and primary chemoresistant (n = 15). Further, after a follow-up of 12-46 months, two groups were identified: no evidence of disease (n = 10) and evidence of disease (n = 25). The primary chemoresistant tumors in comparison to the chemosensitive tumors had significantly lower levels of Fas transcript (p = 0.026), Bax transcript (p = 0.042) and Bcl-2 protein (p = 0.038) and higher levels of Bcl-X(L) (p = 0.040). The apoptotic index revealed a significant inverse correlation only with Bcl-X(L) protein levels (p = 0.003). Patients with evidence of disease at last follow-up in comparison to those with no evidence of disease showed lower Bax transcript (p = 0.012), Bcl-2 protein (p = 0.014) and lower apoptotic index (p = 0.005) and higher Bcl-X(L) protein levels (p = 0.023). In conclusion, Bcl-2 family members and apoptotic index are useful in prediction of response to chemotherapy in EOC. These initial observations need to be validated in large-scale studies.

Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC).

The aim was to determine whether promoter methylation of BRCA1, MGMT, MLH1, RASSF1A, and p16 genes could predict response to platinum-based chemotherapy. Thirty-five subjects with epithelial ovarian cancer (EOC) treated by platinum-based chemotherapy were recruited. Methylation-specific polymerase chain reaction was carried out and the methylation index (MI) was also derived. Response to platinum-based chemotherapy was documented clinically, radiologically, and by serial CA125 levels. Methylated BRCA1 (p = .037) and a higher MI (p = .045) were associated with primary chemosensitivity. A better outcome was predicted by a higher MI (p = .032). In EOC, BRCA1 gene promoter methylation is useful in the prediction of response to chemotherapy.

Serum soluble Fas levels and prediction of response to platinum-based chemotherapy in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is treated mainly by platinum-based combination chemotherapy. Chemotherapy induces apoptosis in which the Fas/Fas ligand pathway is important. Serum soluble Fas (sFas) is a biomarker of this pathway and functionally inhibits Fas-/FasL-mediated apoptosis. In this study, we have investigated the role of sFas in prediction of response to chemotherapy in EOC. Thirty-five patients were recruited and their serum sFas levels were estimated by ELISA at 4 time points-preoperative (sFas1), postoperative (sFas2), midchemotherapy (sFas3) and at the end of chemotherapy (sFas4). The response to chemotherapy was documented clinically, radiologically and by CA-125 levels, based on which, 2 groups were identified: primary chemosensitive (n = 24) and primary chemoresistant (n = 11). Based on the disease status at last follow-up, 2 groups were identified: No Evidence of Disease (n = 15) and Evidence of Disease (n = 20). The primary chemoresistant tumors showed significantly higher median sFas2 levels (p = 0.033) with the sFas2/sFas1 ratio > or =1 (p = 0.001). A multivariate Cox proportional hazards regression model identified sFas2/sFas1 ratio as a significant factor for the prediction of response to platinum-based chemotherapy (p = 0.011). Receiver operating characteristic (ROC) analysis showed that at a ratio of 1.2, sFas2/sFas1 achieved a sensitivity of 82% and specificity of 100% for prediction of chemotherapeutic response. sFas2/sFas1 and sFas3/sFas1 ratio was also higher in patients with evidence of disease (p = 0.018 and p = 0.028, respectively). Progression-free survival rates in patients with sFas2/sFas1 ratio <1 exceeded those with ratio > or =1 (p = 0.004). In conclusion, serum sFas is a useful biomarker for predicting response to platinum-based chemotherapy in EOC.

Second primary in the contralateral breast after treatment of breast cancer.

PURPOSE: To study the potential risk factors for contralateral breast cancer (CBC) in women after treatment of the primary breast cancer. PATIENTS AND METHODS: Between January 1985 and December 1995, records of 1084 breast cancer patients at our institution were analyzed for incidence of CBC. In all the patients a detailed analysis was carried out with respect to age, disease stage, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. The Kaplan-Meier method was used to estimate the acturial rate of CBC. The Cox proportional hazard regression model was used to estimate the relative risk (RR) of CBC. RESULTS: Up to December 2005, the median follow up was 12 years. Overall incidence of CBC was 4%. The 10 and 20 year acturial rate of CBC was 5.6% and 11.3%, respectively. The CBC rate at 10 and 20 year was 5.4% and 10.2%, respectively, for patients with mastectomy only and 5.1% and 9.7%, respectively, in the mastectomy plus RT group (p=0.3). In the subset of patients <45 years of age at the time of treatment, 10 and 20 year acturial rate of CBC was 5% and 9%, respectively, for patients who underwent mastectomy only and 6.3% and 11%, respectively, for patients treated with mastectomy plus RT (RR=1.4, 95% CI: 1.14-1.45, p=0.003). There was statistically significant lower rate of CBC in patients given adjuvant hormonal therapy (8.5%) as compared to those without hormonal therapy (14.3%, p=0.004) at 20 year. Women with family history of breast cancer had highest rate (15.3%) of CBC (RR=1.6, 95% CI: 1.12-1.27) at 20 years. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancy. CONCLUSION: There seems to be little risk of second malignancies in patients treated with mastectomy plus RT using modern techniques, compared with mastectomy only, that was only prevalent in patients <45 years of age. Family history of breast cancer seems to be the highest risk factor for CBC.

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.