Radiotherapy For Cervical Carcinoma Research Articles

MO-0880 Early experiences with CBCT-based online adaptive radiotherapy in cervical carcinoma

MO-0880 Early experiences with CBCT-based online adaptive radiotherapy in cervical carcinoma

Interfraction variations in doses at OARs during three-dimensional high dose rate brachytherapy planning of cervix cancer.

The American Brachytherapy (BT) Society recommends that BT must be included as a component of the definitive radiation therapy for cervical carcinoma because recurrences and complications are decreased when BT is used in addition to external beam radiotherapy. The aim of this study is to quantify the interfraction dose variations (VARacts) during high dose rate (HDR) BT, the effect of variation in dose in terms of excess "unrecognized" dose to OAR and to conclude the reason of the variation in reference of applicator position/geometry versus deformation of the organ at risk (OAR) concerned. Total 30 patients of carcinoma cervix, biopsy proven, between June 2018 and May 2019, were taken for the study. All patients were treated with external beam radiation therapy to a dose of 50 Gy in 25 fractions over 5 weeks, followed by three fractions of HDR intracavitary brachytherapy (ICBT) (7.5 Gy to point A in each fraction) by two-dimensional (2D) X-ray-based planning. Before treatment in the first and last fraction of BT, computed tomography (CT) scan was done for every patient. Then, a 3D-based planning was performed with CT images on our HDR Plus software with image sequence option. VARact was calculated. Rigid image registration of consecutive fraction images was used for quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. The mean contoured rectal volumes for the first and third fractions were 41.49 cc and 44.72 cc, respectively, while the respective volumes for bladder were 9.33 cc and 9.35 cc cm. These differences were statistically insignificant (P value: 0.263 and 0.919 for rectum and bladder, respectively). The mean equivalent dose in 2 Gy fraction (EQD2) bladder D2cc was 5.68 Gy and 5.79 Gy in the first and third fraction ICBT, respectively. The mean EQD2 for the rectal D2cc was 11.63 Gy and 12.85 Gy in the first and third fraction ICBT, respectively. None of the patients had an actual cumulative EQD2 more than 90 Gy for bladder, but 36.66% of the patients had a rectal dose exceeding the tolerance (75 Gy). Regression plots showed that VARhypo alone could predict about 42.2% of the VARact in the rectum and 19.2% of the VARact in the bladder. Thus, the remaining variation was due to the organ deformation-related dose variations between the two fractions. There were no statistically significant variations in the volumes or doses of OAR between the two fractions. However, a significant proportion of patients may have a higher dose to the OAR in the third fraction in the absence of individualized planning. This increase is likely to be more detrimental where higher doses per fraction are used. Variations in OAR doses may be caused by organ deformation and/or changes in applicator placement/geometry.

Treatment of Radiation Enteritis With Fecal Transplantation.

Radiation enteritis (RE) is a frequent complication in patients who undergo pelvic irradiation, and this condition has been increasingly diagnosed. Fecal microbiota transplantation (FMT) is being developed in recent years, and it has remarkable curative effect for the clostridium and inflammatory bowel disease. Herein, we present a case of recurrent RE in a 59-year-old woman with RE 18years after radiotherapy for cervical carcinoma. Fecal microbiota transplantation therapy with intestinal flora from her 18-year-old son was applied and was successful in relieving the symptoms. To the best of our knowledge, this study is the first case report of FMT in a patient with RE.

Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma.

BackgroundRadiotherapy (RT), one of the main treatments for cervical cancer, has tremendous potential for improvement in the efficacy. Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair of DNA strand breaks (DSB). Olaparib (Ola) is a PARP inhibitor that is involved in preventing the release of PARP from RT-induced damaged DNA to potentiate the effect of RT. Although the basic mechanism of Ola’s radiosensitization is well known, the radiosensitization mechanism of its nanomedicine is still unclear. In addition, the lack of tumor tissue targeting is a major obstacle for the clinical success of Ola.Materials and MethodsIn this study, we developed folate-conjugated active targeting olaparib nanoparticles (ATO) and investigated the anti-tumor effect of ATO combined with radiotherapy (RT) in nude mice using cervical cancer xenograft models. We used folate (FA)-conjugated poly (ε-caprolactone)-poly (ethyleneglycol)-poly (e-caprolactone) (PCEC) copolymer to prepare ATO via emulsification/solvent diffusion. Further, we evaluated ATO particle size, potential, encapsulation efficiency, and in vitro release characteristics, and evaluated the shape of ATO via transmission electron microscopy (TEM). We then performed MTT and cell uptake assays to detect cytotoxicity and targeting uptake in vitro. We investigated the anti-tumor properties of ATO in vivo by apoptosis test, 18 F-FDG PET/CT, and immunohistochemical analysis. Finally, the xenografted tumor in nude mice was subjected to RT and/or ATO treatment.ResultsThe results confirmed that ATO in combination with RT significantly inhibited tumor growth and prolonged survival time of tumor-bearing mice. This may be related to the inhibition of tumor proliferation and DNA damage repair and induction of cell apoptosis in vivo.ConclusionThe ATO developed in this study may represent a novel formulation for olaparib delivery and have promising potential for treating tumors with an over-expression of folate receptors.

Measurement of Cervical Regression and Optimizing Brachytherapy Schedule Concurrently with External Beam Radiation Therapy in Cervical Carcinoma.

IntroductionThis study aimed to measure cervical regression during external beam radiation therapy (EBRT) and optimize the scheduling of brachytherapy concurrently with EBRT.MethodsFifty consecutive patients with carcinoma of the cervix stage IIA to IIIB received concurrent chemoradiotherapy with weekly Cisplatin 40 mg/m2. Cervical regression was evaluated using serial CT scans obtained before and during concurrent chemoradiotherapy (on the third, fourth, and fifth weeks). High dose rate brachytherapy was introduced after 30Gy of EBRT. A total of 25.5Gy in three fractions were delivered during the third, fourth, and fifth weeks of EBRT. Cervical volumes were recorded from the CT scan for cervical regression.ResultsThe mean cervical volume at baseline (i.e., before the start of treatment) was 85.53 cubic centimetres (cc). The mean cervical volumes at the end of the third, fourth, and fifth week were 28.95cc, 24.92cc, and 21.80cc, respectively. The mean cervical regression from baseline to the end of the third, fourth, and fifth week was 60%, 65%, and 69%, respectively. The time for 50% cervical regression was calculated to be 18 days and occurred around 27Gy of EBRT.ConclusionMore than 50% of cervical regressions occur at the end of the third week (i.e., after delivery of 30Gy of EBRT), so it is optimal to introduce brachytherapy at the end of the third week. A conventional point-based plan can cover the high-risk clinical target volume (HRCTV) if the volume is <25cc, but an HRCTV >25cc may be well covered with optimization or a combination of intracavitary and interstitial brachytherapy.

Endometrial cancer after radiation therapy for cervical carcinoma: A radiological approach

Clinical and pathological aspects of endometrial cancers that develop after radiation therapy for cervical carcinoma have been studied for years but their imaging features have not yet been described.To determine these features, we performed a retrospective study that included all patients of our institution that were diagnosed with an endometrial cancer after being submitted to radiation therapy for cervical cancer and that performed computed tomography (CT) or magnetic resonance (MR) imaging at the time of the diagnosis, in a period of 11 years.We found 13 patients meeting these inclusion criteria. A wide range of morphologies were observed: single solid tumors (46%); single mixed tumors (15%); large heterogeneous multifocal tumors (15%) and multifocal small polypoid tumors (15%). Large tumors were frequent at presentation, with 65% of the lesions measuring more than 5 cm (mean, 7.4 cm; range, 1.2–14.9 cm). Hematometra was a striking feature that was present in 85% of the cases, with a mean volume of 318 mL and was associated in 91% of the cases with cervical stenosis, a known complication of pelvic radiotherapy that could justify a delay in symptoms presentation. Post-radiotherapy changes and hematometra limited the utility of MR imaging in local staging. Distant metastases could be promptly diagnosed with CT or MR imaging and were observed in 42% of the patients.These rare heterogeneous tumors should be considered after radiotherapy for cervical carcinoma, especially when hematometra is observed. Aggressive histological presentations and delayed symptoms due to cervical stenosis are responsible for an unfavorable prognosis.

Value of Dynamic Contrast-enhanced and Diffusion-weighted MR Imaging in the Detection of Pathologic Complete Response in Cervical Cancer after Neoadjuvant Therapy: A Retrospective Observational Study.

Purpose To evaluate the association between dynamic contrast material-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance (MR) imaging with pathologic complete response after preoperative combined chemotherapy and radiation therapy for cervical carcinoma and evaluate the risk of local recurrence. Materials and Methods The institutional ethics committee approved the study and waived the requirement to obtain informed consent. The study comprised 52 patients with locally advanced carcinoma, treated first with combined chemotherapy and radiation therapy, who underwent MR imaging before final surgery between June 2011 and July 2015. Three radiologists evaluated conventional, DW, and DCE MR images to identify a complete response. The standard of reference was surgical-pathologic findings. Results An initial increase in signal intensity on DCE MR images that was greater in the cervical lesion than in the myometrium was defined as time-signal intensity curve type B and showed a significant association with incomplete response (P = .0004). DCE MR imaging parameters (ie, maximum slope enhancement, area under the gadolinium concentration-time curve during the first 90 seconds after gadolinium injection [AUGC90], and volume transfer constant [Ktrans]) and a low signal intensity on apparent diffusion coefficient (ADC) maps were significantly associated with an incomplete response (P = .027, P = .041, P = .037, and P = .032, respectively). A mean ADC of 0.0014 m2/sec or less (hazard ratio [HR] = 8.3), low ADC signal intensity (HR = 7.3), high signal intensity at DW imaging (HR = 7.1), and time-signal intensity curve type B (HR = 4.3) were associated with earlier recurrence (P < .05). Excellent agreement between readers was found for time-signal intensity curve analysis (κ > 0.9) and the following parameters: AUGC90, Ktrans, and maximum slope enhancement (intraclass correlation coefficient, >0.9). Conclusion DCE MR imaging parameters, especially the time-signal intensity curve, and DW imaging are associated with complete response and incomplete response and could potentially help oncologists with management decisions. Moreover, DCE and DW MR imaging could help oncologists accentuate the follow-up for patients with a high risk of local recurrence to assess for recurrence. © RSNA, 2017 Online supplemental material is available for this article.

The stratification of severity of acute radiation proctopathy after radiotherapy for cervical carcinoma using diffusion-weighted MRI

ObjectiveTo determine whether diffusion-weighted imaging (DWI) can be used for quantitatively evaluating severity of acute radiation proctopathy after radiotherapy for cervical carcinoma. Materials and methodsOne hundred and twenty-four patients with cervical carcinoma underwent MR examination including DWI before and after radiotherapy. Acute radiation proctopathy was classified into three groups (grade 0, grade I–II and grade III–IV) according to Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG). The pretreatment ADC (ADCpre), ADC after treatment (ADCpost) and ADC change (ΔADC) were compared among three groups. In addition, acute radiation proctopathy was classified into good-prognosis group and poor-prognosis group. ADCpre, ADCpost and ΔADC were compared between two groups. For DWI parameter that had significant difference, discriminatory capability of the parameter was determined using receiver operating characteristics (ROC) analysis. ResultsADCpost and ΔADC were higher in grade I–II group than in grade 0 group (p<0.05), yielding a sensitivity of 79.3% and specificity of 69.4% for ADCpost, and 85.1%, 72.3% for ΔADC for discrimination between two groups. ADCpost and ΔADC were higher in grade III–IV group than in grade I–II group (p<0.05), yielding a sensitivity of 80.3% and specificity of 72.5% for ADCpost, and 84.1%, 74.5% for ΔADC for discrimination between two groups. ADCpost and ΔADC were higher in poor-prognosis group than in good-prognosis group (p<0.05), yielding a sensitivity of 79.5% and specificity of 73.4% for ADCpost, and 87.2%, 78.3% for ΔADC for discrimination between two groups. ConclusionDiffusion-weighted MRI can be used for quantitative stratification of severity of acute radiation proctopathy, which serves as an important basis for appropriate timely adjustment of radiotherapy for cervical carcinoma in order to maximally reduce the radiation injury of rectum.

Research advances in preservation of ovarian function during radiotherapy for cervical carcinoma

At present, reports at home and abroad suggest a low probability of successful preservation of ovarian endocrine function after ovarian shift radiotherapy. After radiotherapy for cervical carcinoma, the ovarian function is associated with various factors, such as radiotherapy dose and method, patient′s age, shift position, and concurrent chemotherapy drugs. Therefore, as for each patient, the dose to the ovarian tissue should be controlled within the individual dose limit to effectively preserve the ovarian function. Key words: Cervical neoplasms/radiotherapy; Ovarian function; Ovarian protection

EP-1973: MRI-guided brachytherapy and 3D/IMRT radiotherapy for cervical carcinoma. A prospective study

EP-1973: MRI-guided brachytherapy and 3D/IMRT radiotherapy for cervical carcinoma. A prospective study

Endometrial Cancer Occurring 27 Years after Radiation Therapy for Cervical Carcinoma

Endometrial Cancer Occurring 27 Years after Radiation Therapy for Cervical Carcinoma

SU-E-J-88: The Study of Setup Error Measured by CBCT in Postoperative Radiotherapy for Cervical Carcinoma

Purpose: To compare two registration methods in the CBCT guided radiotherapy for cervical carcinoma, analyze the setup errors and registration methods, determine the margin required for clinical target volume(CTV) extending to planning target volume(PTV). Methods: Twenty patients with cervical carcinoma were enrolled. All patients were underwent CT simulation in the supine position. Transfering the CT images to the treatment planning system and defining the CTV, PTV and the organs at risk (OAR), then transmit them to the XVI workshop. CBCT scans were performed before radiotherapy and registered to planning CT images according to bone and gray value registration methods. Compared two methods and obtain left-right(X), superior-inferior(Y), anterior-posterior (Z) setup errors, the margin required for CTV to PTV were calculated. Results: Setup errors were unavoidable in postoperative cervical carcinoma irradiation. The setup errors measured by method of bone (systemic ± random) on X(1eft.right),Y(superior.inferior),Z(anterior.posterior) directions were(0.24±3.62),(0.77±5.05) and (0.13±3.89)mm, respectively, the setup errors measured by method of grey (systemic ± random) on X(1eft-right), Y(superior-inferior), Z(anterior-posterior) directions were(0.31±3.93), (0.85±5.16) and (0.21±4.12)mm, respectively.The spatial distributions of setup error was maximum in Y direction. The margins were 4 mm in X axis, 6 mm in Y axis, 4 mm in Z axis respectively.These two registration methodsmore » were similar and highly recommended. Conclusion: Both bone and grey registration methods could offer an accurate setup error. The influence of setup errors of a PTV margin would be suggested by 4mm, 4mm and 6mm on X, Y and Z directions for postoperative radiotherapy for cervical carcinoma.« less

Pseudoxanthomatous salpingitis as an ex vivo model of fallopian tube serous carcinogenesis: a clinicopathologic study of 49 cases.

Iron is a well-documented carcinogen based on both animal models and observational studies in humans. There are limited published data on pseudoxanthomatous salpingitis, an uncommon condition characterized by the accumulation of histiocytes containing iron and iron-related compounds-lipofuscin and hemosiderin-in the lamina propria of the fallopian tube. The clinical and pathologic features of 49 consecutive cases were evaluated. The mean patient age was 53. A history of endometriosis was found in 20%, infertility in 17%, and tubal ligation in 7%. Thirteen (27%) had endometrial cancer and 2 patients had prior radiation therapy for cervical carcinoma. Histologic evidence of endometriosis other than tubal pigment deposition was identified in 65%, and in the fallopian tubes in 35%. Pigment deposition was unilateral in 65% and multifocal or diffuse in 80%. Plasma cells, eosinophils, and neutrophils were present in the tubal lamina propria in 57%, 18%, and 24%, respectively. Hydrosalpinx was present in 51%. An iron stain was positive in pseudoxanthoma cells lacking hemosiderin in 14 of 18 cases (78%). By immunohistochemistry, 2 of 22 cases displayed p53 signatures. The Ki67 proliferation index was elevated (>10%) in 11 of 22 cases, with a mean index of 32% in those cases. An elevated proliferation index did not correlate with inflammation. In summary, these findings characterize the clinical and pathologic features of pseudoxanthomatous salpingitis and confirm its close association with endometriosis, occasional association with radiation therapy, and the presence of iron in the histiocytes. In view of the evolving paradigm shift implicating the fallopian tubal epithelium as the site of origin of high-grade extrauterine serous carcinoma, the presence of iron and iron-related compounds in the fallopian tube provides an opportunity to study the early events in high-grade serous carcinogenesis in a setting characterized by a well-documented carcinogen in close anatomic proximity to the putative epithelium of origin.

A randomized controlled clinical trial of formalin for treatment of chronic hemorrhagic radiation proctopathy in cervical carcinoma patients.

Chronic hemorrhagic radiation proctopathy is not uncommon after radiotherapy for cervical carcinoma. The outcomes of several treatments have been variable. Many studies demonstrate that topical treatment with 4 % formalin is effective and safe. However, a nonrandomized control study showed a high response rate and good tolerance in chronic radiation proctopathy patients treated with 10 % formalin. The optimal concentration of formalin therefore remains unclear. To compare the effectiveness and safety of 4 and 10 % formalin for the treatment of chronic hemorrhagic radiation proctopathy, a prospective trial was conducted at the Department of Gynecology of the Affiliated Hospital of Binzhou Medical College from January 2009 to December 2012. One hundred and twenty patients with chronic hemorrhagic radiation proctopathy following radiotherapy for cervical carcinoma were recruited and randomized to receive 4 or 10 % formalin. A standard protocol was followed for formalin application. Symptom and rectoscopy scores were evaluated before and at 12 weeks after treatment. In the 4 % formalin group, 49 (86.0 %) and 53 (91.4 %) patients showed an improvement in symptom score and rectoscopy score, respectively (P = 0.36). Symptom and rectoscopy scores decreased significantly after treatment in both the 4 % formalin group and the 10 % formalin group (P < 0.001). Symptom score was correlated with rectoscopy score (P < 0.001). More patients in the 10 % group suffered treatment-related complications than did those in the 4 % group (P = 0.03). For the treatment of chronic hemorrhagic radiation proctopathy, 4 % should be the preferred formalin concentration.

Advance in radiotherapy of cervical carcinoma

Radiotherapy plays a crucial role in cervical cancer.Intensity modulated radiation therapy is widely used gradually,which allows the photon beam within each field to be modulated and therefore improves the dose distribution by maximizing target coverage and minimizing the damage to normal tissue.Concurrent radiochemotherapy plus brachytherapy are standard therapeutic methods for local advanced cervical cancer. Key words: Cervical neoplasms; Radiotherapy; Brachytherapy

Dosimetric analysis of intensity-modulated radiotherapy in cervical carcinoma

Objective To compare the dosimetric difference on organ at risk (OAR) in intensitymodulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) in treatment with cervical carcinoma. Methods 36 cases of cervical cancer patients accepted radiotherapy both on IMRT and 3D-CRT in the same time,clinical target volume (CTV) focused on primary tumor and its lymphatic drainage area.Lymphatic drainage area was determined as follows:1.0 cm extension were added to the margin of pelvic vessels,the obturator lymph nodes region was extended by 1.8 cm from the pelvis inner margin.CTV does not include pelvic tissue. Data of dose distribution and irradiation volume of OAR on the basis of distributing on 45 Gy and 50 Gy were analyzed individually. The margins of planning target volume (PTV) was obtained based on CTV margins by which added 1.0 cm extension in inferior and superior directions,0.7 cm were added in all other directions. Results With the comparison of variety on irradiation volume of organs at risk (OAR) by DVH in both groups,underlying the treatment dose 45 Gy,the individual volume of D30,D40 and D45 were all lesser in IMRT plan than that of 3D-CRT plan. Even on the dose 50 Gy at pelvic wall lymph nodes regions,the volume of OAR was lesser than that in 3D-CRT plan.Conclusion In the radiotherapy of cervical cancer,IMRT should have improved protections for tumor surrounding OAR which has domestic superiority in clinical application. Key words: Uterine cervical neoplasms; Radiotherapy,intensity-modulated; Radiotherapy dosage; Organs at risk

Dosimetric comparison of high dose rate brachytherapy and intensity-modulated radiation therapy for cervical carcinoma

Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies. A dosimetric intercomparison of high dose rate intracavitary brachytherapy (HDR_BT) and intensity-modulated radiotherapy in cervical carcinoma has been made in the present study. CT scan images of 10 patients treated with HDR_BT were used for this study. A sliding-window IMRT (IMRT_SW) and step-and-shoot IMRT plans were generated using 6-MV X-rays. The cumulative dose volume histograms of target, bladder, rectum and normal tissue were analyzed for both techniques and dose distributions were compared. It was seen that the pear-shaped dose distribution characteristic of intracavitary brachytherapy with sharp dose fall-off outside the target could be achieved with IMRT. The integral dose to planning target volume was significantly higher with HDR_BT in comparison with IMRT. Significant differences between the two techniques were seen for doses to 1 cc and 2 cc of rectum, while the differences in 1 cc and 2 cc doses to bladder were not significant. The integral doses to the nontarget critical and normal structures were smaller with HDR_BT and with IMRT. It is concluded that IMRT can be the choice of treatment in case of non-availability of HDR brachytherapy facilities or when noninvasive treatments are preferred

Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm 3) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5–10% in 26 patients, and 10–14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

Radiation-induced chondrosarcomas: A case report with review of literature

Radiation therapy has become an important component of various cancer treatments. The development of second malignancy as a result of radiation therapy is a well-known sinister complication. However, radiation-induced sarcomas (RIS) are rare complications of radiation therapy. The timescale between completion of the radiotherapy and the development of a second malignancy, known as the latent period, can vary widely from as little as 5 years to 50 years later. Radiation-induced sarcomas per se are very rare and those with histomorphology of chondrosarcomas are even rarer. We report a rare case of RIS of left iliac bone in a 62-year-old lady after combined chemotherapy and external beam radiation therapy for cervical carcinoma (stage IIb). This case is being reported for its extreme rarity, vivid histology and clinical presentation.

Japanese Patterns of Care Study of Definitive Radiotherapy for Cervical Carcinoma among Three Surveys

Japanese Patterns of Care Study of Definitive Radiotherapy for Cervical Carcinoma among Three Surveys