Bhavana Rai

Dose-effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study

BACKGROUND/PURPOSE To identify risk factors for vaginal stenosis and to establish a dose-effect relationship for image-guided brachytherapy in locally advanced cervical cancer. MATERIALS/METHODS Patients from the ongoing EMBRACE study with prospectively assessed morbidity (CTCAEv3.0) at baseline and at least one follow-up were selected. Patient-, disease- and treatment characteristics were tested as risk factors for vaginal stenosis G ⩾ 2 in univariate and multivariable analyses (Cox proportional hazards model) and a dose-effect curve was deduced from the estimates. The ICRU rectum point was used to derive the recto-vaginal reference point dose. RESULTS In 630 patients included (median follow-up 24months), 2-year actuarial estimate for vaginal stenosis G ⩾ 2 was 21%. Recto-vaginal reference point dose (HR=1.025, p=0.029), external beam radiotherapy (EBRT) dose >45 Gy/25 fractions (HR=1.770, p=0.056) and tumor extension in the vagina (HR=2.259, p ⩽ 0.001) were risk factors for vaginal stenosis, adjusted for center reporting effects. Based on the model curve, the risk was 20% at 65 Gy, 27% at 75 Gy and 34% at 85 Gy (recto-vaginal reference point dose). CONCLUSION Keeping the EBRT dose at 45 Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis. A planning aim of ⩽65 Gy EQD2 (EBRT+brachytherapy dose) to the recto-vaginal reference point is therefore proposed.

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.

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.

Breast cancer in males: A PGIMER experience

AIM Male breast cancer is a rare disease representing 1% of all breast cancers and less than 1% of all cancers in men. Because of its rarity, carcinoma breast has not been studied extensively and this prompted us to carry out this retrospective study. The aim of the study was to observe the clinical and pathological features, evaluate the prognostic factors and to co-relate the outcome in patients of male breast cancer. MATERIALS AND METHODS Thirty patients of male breast cancer treated in the department of radiotherapy from year 1996-2000 were retrospectively analyzed. RESULTS The actuarial five- year disease free survival was 40%. Three out of 30 i.e. 10% patients had loco-regional recurrence and all of them had locally advanced disease at presentation. Distant metastasis occurred in 9 patients of whom 6 patients had T3-T4 tumor and 1 patient had T1-T2 tumor. CONCLUSION Modified radical mastectomy followed by external radiation therapy is the standard treatment for male breast cancer. Hormone therapy, as an adjuvant treatment, is the first line approach in a majority of patients and chemotherapy is reserved for patients with poor prognostic factors.

A volumetric analysis of GTVD and CTVHR as defined by the GEC ESTRO recommendations in FIGO stage IIB and IIIB cervical cancer patients treated with IGABT in a prospective multicentric trial (EMBRACE)

PURPOSE To quantify the gross tumor volume at diagnosis (GTVD) and high-risk clinical target volume (CTVHR) at brachytherapy (BT) and describe subgroups of patients with different patterns of response to chemoradiotherapy (CRT) in patients with FIGO stage IIB and IIIB cervical cancer treated with image-guided adaptive brachytherapy (IGABT). Additionally, to evaluate the feasibility of IGABT achieving adequate target coverage in these groups. MATERIALS AND METHODS Patients with FIGO stage IIB and IIIB cervical cancer enrolled in the EMBRACE study were analyzed. T2-weighted MRI scans were obtained at diagnosis and at BT. GTVD and CTVHR were defined as per the GEC ESTRO recommendations. Patients were classified taking into account that initial tumor volume and response to CRT represented by the volume of residual disease (CTVHR) and extent of residual parametrial disease are all major factors determining local dose delivery by BT, local control, and overall disease outcome. These factors were quantified applying the following criteria: (1) volume of the GTVD relative to the median volume of the GTVD; (2) the ratio (R) of CTVHR to GTVD for each patient; (3) the extent of residual parametrial disease at the time of BT. Accordingly, patients were classified into six groups (G1-G6): stage IB1-like tumors (G1), tumors with good response and any size (G2), small tumors with moderate response (G3), large tumors with moderate response (G4), tumors with poor response (G5) and those with progressive disease (G6). Tumor and treatment characteristics were then compared among the first five groups (only 3 patients were allocated to G6). RESULTS A total of 481 patients were evaluated. The number of patients in the 6 groups were 55, 78, 123, 147, 75 and 3, respectively. The mean (SD) GTVD was 43.6 (32.8)cm3 and the mean (SD) CTVHR was 31.6 (16.1)cm3. The mean GTVD and CTVHR were 12.6cm3 and 23.7cm3 in G1 (R>1.1), 47.5cm3 and 25.3cm3 in G2 (R<0.9), 23.9 cm3 and 29.9cm3 in G3 (R 0.9-1.1), 73.4cm3 and 38.5cm3 in G4 (R 0.9-1.1), 79.4cm3 and 59.5cm3 in G5 (R>1.1), respectively. Parametrial disease extent at BT was as follows: no involvement in G1 and G2, proximal at most in G3 and G4, distal or to the pelvic wall in G5, progressive in G6. The use of interstitial needles was progressively higher among the groups (mean 0, 0, 2, 3, 6 in G1-5, P<0.001). The mean GTVBT D100 in G1-5 was 103.1Gy, 91.8Gy, 93.5Gy, 88.3Gy and 87.1Gy. The mean CTVHR D90 in G1-5 was 95.1Gy, 92.1Gy, 92.6Gy, 87.6Gy and 88.4Gy. CONCLUSIONS In patients with FIGO stage IIB and IIIB disease, intra-FIGO stage heterogeneity and overlap between the two stages exist with respect to tumor volume, treatment response and extent of parametrial disease at BT. Taking into account GTVD, parametrial disease at BT and the ratio of CTVHR/GTVD, five major groups exist. These enable prediction of GTVBT and CTVHR dose coverage through BT. IGABT, as performed in EMBRACE, accommodates to a considerable degree for the different variants of tumor regression in these groups through adaptation of the treatment technique including the use of needles. However, major variations remain at present with regard to dose to GTVBT and to CTVHR, which are most pronounced in G4 and G5. This new classification will be validated in future in regard to clinical outcome in EMBRACE.

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.

Bladder-rectum spacer balloon in high-dose-rate brachytherapy in cervix carcinoma.

PURPOSE To compare bladder and rectum doses with the use of a bladder-rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. METHODS AND MATERIALS This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm(3), 1-cm(3), 2-cm(3), 5-cm(3), and 10-cm(3) volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. RESULTS A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm(3), 1 cm(3), 2 cm(3), 5 cm(3), and 10 cm(3) and ICRU bladder point. Statistically significant dose reductions to 0.1-cm(3), 1-cm(3), and 2-cm(3) volumes for rectum were observed with the BRSB. No significant differences in 5-cm(3) and 10-cm(3) volumes and ICRU rectum point were observed. CONCLUSION A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of variable sizes are recommended for patients with a less spacious vaginal cavity.

The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies

Graphical abstract

Assessment of Parametrial Response by Growth Pattern in Patients With International Federation of Gynecology and Obstetrics Stage IIB and IIIB Cervical Cancer: Analysis of Patients From a Prospective, Multicenter Trial (EMBRACE)

PURPOSE To assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of image-guided adaptive brachytherapy. METHODS AND MATERIALS Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype on magnetic resonance imaging (expansive and infiltrative), and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at brachytherapy was evaluated, and the response to chemo-radiotherapy was classified as good, moderate, or poor. The response grade was compared between the 2 groups and analyzed with regard to tumor volumes, and dosimetric parameters. RESULTS A total of 452 patients were evaluated, of whom 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease, as indicated by a higher rate of FIGO stage IIIB disease, as well as radiologic evidence of extension into the distal parametrial space and to the pelvic side wall on magnetic resonance imaging. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%; P=.02), and poor response was more common in the infiltrative group (11% and 19%; P=.02). Mean gross tumor volume at diagnosis was equal in both groups (51.7 cm(3)). The high-risk clinical target volume was larger in infiltrative tumors (37.9 cm(3) vs 33.3 cm(3), P=.005). The mean high-risk clinical target volume D90 was slightly higher in expansive tumors (92.7 Gy and 89.4 Gy, P<.001). CONCLUSION Infiltrative tumors are more advanced at presentation and respond less favorably to chemo-radiotherapy when compared with expansive tumors that are more or less equivalent in size. The use of image-guided adaptive brachytherapy allows achieving reasonably high doses in both groups.

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 (D2cc,D1cc,D0.1cc, and D5cc 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 2 mm 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 registration 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. PACS number: 87.55.km