Optimisation and evaluation of the random forest model in the efficacy prediction of chemoradiotherapy for advanced cervical cancer based on radiomics signature from high-resolution T2 weighted images.

PURPOSE: Our objective was to establish a random forest model and to evaluate its predictive capability of the treatment effect of neoadjuvant chemotherapy-radiation therapy. METHODS: This retrospective study included 82 patients with locally advanced cervical cancer who underwent scanning from March 2013 to May 2018. The random forest model was established and optimised based on the open source toolkit scikit-learn. Byoptimising of the number of decision trees in the random forest, the criteria for selecting the final partition index and the minimum number of samples partitioned by each node, the performance of random forest in the prediction of the treatment effect of neoadjuvant chemotherapy-radiation therapy on advanced cervical cancer (> IIb) was evaluated. RESULTS: The number of decision trees in the random forests influenced the model performance. When the number of decision trees was set to 10, 25, 40, 55, 70, 85 and 100, the performance of random forest model exhibited an increasing trend first and then a decreasing one. The criteria for the selection of final partition index showed significant effects on the generation of decision trees. The Gini index demonstrated a better effect compared with information gain index. The area under the receiver operating curve for Gini index attained a value of 0.917. CONCLUSION: The random forest model showed potential in predicting the treatment effect of neoadjuvant chemotherapy-radiation therapy based on high-resolution T2WIs for advanced cervical cancer (> IIb).

Volume computed tomography perfusion as a predictive marker for treatment response to concurrent chemoradiotherapy in cervical cancer: a prospective study.

BACKGROUND: Computed tomography perfusion (CTP) can provide information on blood perfusion as a reliable marker of tumor response to therapy. PURPOSE: To assess the role of volume CTP (vCTP) parameters in predicting treatment response to concurrent chemoradiotherapy (CCRT) for cervical cancer. MATERIAL AND METHODS: Thirty-three patients with cervical cancer underwent vCTP. Three CTP parameters of cervical cancer-including arterial flow (AF), blood volume (BV), and permeability surface (PS)-were measured in two different ways: the region of interest incorporating the "local hot" with the highest enhancement and "cold spot" with the lowest enhancement; and "whole-tumor" measurements. The patients were divided into non-residual and residual tumor groups according to the short-term response to treatment. The clinical and perfusion parameters were compared between the two groups. RESULTS: There was no significant difference in age, body mass index, FIGO stage, pathological grade, or pretreatment tumor size between the two groups (P > 0.05). The non-residual tumor group had higher pretreatment AF in high-perfusion and low-perfusion subregions than the residual tumor group (P <0.05), but the AF in whole-tumor regions was not different between the two groups (P > 0.05). There were no differences in BV and PS between the two groups (P > 0.05). The diagnostic potency of AF in the low-perfusion subregion was higher than that in the high-perfusion subregion. CONCLUSION: vCTP parameters are valuable for the prediction of short-term effects. The AF in the low-perfusion subregion was a more effective index for predicting treatment response to CCRT of cervical cancer.

LATE RADIATION TOXICITY AFTER RADICAL RADIOTHERAPY FOR GENITAL CANCER. / PIZNIa PROMENEVA TOKSYChNIST' PISLIa RADYKAL'NOÏ RADIOTERAPIÏ RAKU GENITALII.

Radiation therapy for malignant tumors of the female genital area, even with the use of modern radiotherapy equipment and dosimetric planning, causes the development of local radiation changes. An approach involving methodsof general and local exposure is used in their treatment. One of the most promising directions is the creation of optimal combinations of medicines (in the form of ointments, gels, aerosols, suppositories, etc.), which have a therapeutic effect on the inflammatory process. The article reflects the clinical course and stage of occurrence of late radiation reactions of the skin, vaginal/cervix mucosa, bladder, and intestines, as well as the features of their treatment.Literary data and own practical experience in the treatment of radiation complications are presented. Whenreviewing the topic under study, it could be concluded that the leading cause of the development of local radiationdamage is the errors in the planning and implementation of radiation therapy, when high absorbed doses thatexceed the tolerance of healthy tissues are used. Another reason for this is the poor accounting for dose distribution of ionizing radiation in tissues, the presence of concomitant diseases in patients, and the underestimation ofthe long-term effects of radiation.

Prognostic value of post-radiation serum squamous cell carcinoma antigen and primary tumor regression for cervical squamous cell carcinoma.

OBJECTIVE: In this study, we determined the prognostic values of magnetic resonance imaging (MRI)-based primary tumor regression and serum squamous cell carcinoma antigen (SSCC-Ag) levels 4 weeks after definitive radiotherapy (RT) in cervical squamous cell carcinoma (CSCC) patients. METHODS: This was a retrospective study involving 218 patients with histologically confirmed CSCC (stages IB-IVA). All the patients received definitive RT. Pre- and post-RT pelvic MRI and SSCC-Ag levels were measured. Locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated, and possible OS prognostic factors were analyzed. RESULTS: The median follow-up time was 25.57 (1.73-58.93) months. Thirty-six and 68 patients died and experienced recurrence, respectively, and the primary tumors of 130 (59.6%) and 88 (40.4%) patients exhibited complete response (CR) and non-CR, respectively. The 3-year OS, DFS, LRC, and DMFS rates were significantly higher in the CR than in the non-CR patients (85.2% vs. 67.9%, 78.9% vs. 39.0%, 93.4% vs. 63.8%, and 83.4% vs. 54.5%, respectively; p< 0.05). The 3-year OS, DFS, LRC, and DMFS rates were significantly lower in the patients with high post-RT SSCC-Ag levels than in those with low post-RT SSCC-Ag levels (38.0% vs. 83.9%, 21.2% vs. 66.3%, 73.0% vs. 84.9%, and 26.5% vs. 79.0%, respectively; p<0.05). Multivariate analyses indicated that SSCC-Ag levels were an independent OS predictor (HR: 5.749, 95% CI: 2.598-12.723, p< 0.001). CONCLUSION: Post-RT SSCC-Ag levels are OS independent prognostic factors in CSCC patients receiving RT. Timely and optimized treatment plans for CSCC patients after 4 weeks of RT are necessary when patients with persistent tumor and/or positive SSCC-Ag.

Treatment planning comparison of volumetric modulated arc therapy employing a dual-layer stacked multi-leaf collimator and helical tomotherapy for cervix uteri.

PURPOSE: To ascertain the dosimetric performance of a new delivery system (the Halcyon system, H) equipped with dual-layer stacked multi-leaf collimator (MLC) for risk-adapted targets in cervix uteri cancer patients compared to another ring-based system in clinical operation (Helical Tomotherapy, HT). METHODS: Twenty patients were retrospectively included in a treatment planning study (10 with positive lymph nodes and 10 without). The dose prescription (45Gy to the primary tumour volume and a simultaneously integrated boost up to 55Gy for the positive patients) and the clinical planning objectives were defined consistently as recommended by an ongoing multicentric clinical trial. Halcyon plans were optimised for the volumetric modulated arc therapy. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms. RESULTS: The coverage of the primary and nodal target volumes was comparable for both techniques and both subsets of patients. The primary planning target volume (PTV) receiving at least 95% of the prescription isodose ranged from 97.2 ± 1.1% (node-negative) to 99.1 ± 1.2% (node-positive) for H and from 96.5 ± 1.9% (node-negative) to 98.3 ± 0.9% (node-positive) for HT. The uncertainty is expressed at one standard deviation from the cohort of patient per each group. For the nodal clinical target volumes, the dose received by 98% of the planning target volume ranged 55.5 ± 0.1 to 56.0 ± 0.8Gy for H and HT, respectively. The only significant and potentially relevant differences were observed for the bowels. In this case, V40Gy resulted 226.3 ± 35.9 and 186.9 ± 115.9 cm3 for the node-positive and node-negative patients respectively for Halcyon. The corresponding findings for HT were: 258.9 ± 60.5 and 224.9 ± 102.2 cm3. On the contrary, V15Gy resulted 1279.7 ± 296.5 and 1557.2 ± 359.9 cm3 for HT and H respectively for node-positive and 1010.8 ± 320.9 versus 1203.8 ± 332.8 cm3 for node-negative. CONCLUSION: This retrospective treatment planning study, based on the dose constraints derived from the Embrace II study protocol, suggested the essential equivalence between Halcyon based and Helical Tomotherapy based plans for the intensity-modulated rotational treatment of cervix uteri cancer. Different levels of sparing were observed for the bowels with H better protecting in the high-dose region and HT in the mid-low dose regions. The clinical impact of these differences should be further addressed.

External beam patient dose verification based on the integral quality monitor (IQM®) output signals.

BACKGROUND: The Integral Quality Monitor (IQM®) can essentially measure the integral fluence through a segment and provide real-time information about the accuracy of radiation delivery based on comparisons of measured segment signals and pre-calculated reference values. However, the present IQM chamber cannot calculate the dose in the patient. AIM: This study aims to make use of IQM field output signals to calculate the number of monitor units (MUs) delivered through an arbitrary treatment field in order to convert Monte Carlo (MC)-generated dose distributions in a patient model into absolute dose. METHODS: XiO and Monaco treatment planning systems (TPSs) were used to define treatment beam portals for cervix and esophagus conformal radiotherapy as well as prostate intensity-modulated radiotherapy for the translation of patient and beam setup information from DICOM to DOSXYZnrc. The planned beams were simulated in a patient model built from actual patient CT images and each simulated integral field/segment was weighted with its MUs before summation to get the total dose in the plan. The segment beam weights (MUs) were calculated as the ratio of the open-field IQM measured signal and the calculated signal per MU extracted from chamber sensitivity maps. These are the actual MUs delivered not just MUs set. The beam weighting method was evaluated by comparing weighted MC doses with original planned doses using profile and isodose comparisons, dose difference maps, γ analysis and dose-volume histogram (DVH) data. RESULTS: γ pass rates of up to 98% were found, except for the esophagus plan where the γ pass rate was below 45%. DVH comparisons showed good agreement for most organs, with the largest differences observed in low-density lung. However, these discrepancies can result from differences in dose calculation algorithms or differences in MUs used for dose weighting planned by the TPS and MUs calculated using IQM field output signals. To test this, a 4-field box DOSXYZnrc MC simulation weighted with planned (XiO) MUs was compared with the same simulation weighted with IQM-based MUs. Dose differences of up to 5% were found on the isocentre slice. For XiO versus MC, up to 7% dose differences were found, indicating additional error due to limitations of XiO's superposition algorithm. Dose differences between MC Monaco and MC EGSnrc were less than 3%. CONCLUSIONS: The most valuable comparison was MC versus MC as it eliminated algorithm discrepancies and evaluated dose differences precisely according to beam weighting. For XiO TPS, care must be taken as dose differences may also arise due to limitations in XiO's planning software, not merely due to differences in MUs. Overall, the IQM was successfully used to compute beam dose weights to accurately reconstruct the patient dose using unweighted MC beams. Our technique can be used for pre-treatment QA provided each segment output is known and an accurate linac source model is available.

Evaluation of rectal dose discrepancies between planned and in vivo dosimetry using MOSkin detector and PTW 9112 semiconductor probe during 60Co HDR CT-based intracavitary cervix brachytherapy.

PURPOSE: Dose to the rectum during brachytherapy treatment may differ from an approved treatment plan which can be quantified with in vivo dosimetry (IVD). This study compares the planned with in vivo doses measured with MOSkin and PTW 9112 rectal probe in patients undergoing CT based HDR cervical brachytherapy with Co-60 source. METHODS: Dose measurement of a standard pear-shaped plan carried out in phantom to verify the MOSkin dose measurement accuracy. With MOSkin attached to the third diode, RP3 of the PTW 9112, both detectors were inserted into patients' rectum. The RP3 and MOSkin measured doses in 18 sessions as well as the maximum measured doses from PTW 9112, RPmax in 48 sessions were compared to the planned doses. RESULTS: Percentage dose differences ΔD (%) in phantom study for two MOSkin found to be 2.22 ± 0.07% and 2.5 ± 0.07%. IVD of 18 sessions resulted in ΔD(%) of -16.3% to 14.9% with MOSkin and ΔD(%) of -35.7% to -2.1% with RP3. In 48 sessions, RPmax recorded ΔD(%) of -37.1% to 11.0%. MOSkin_measured doses were higher in 44.4% (8/18) sessions, while RP3_measured were lower than planned doses in all sessions. RPmax_measured were lower in 87.5% of applications (42/47). CONCLUSIONS: The delivered doses proven to deviate from planned doses due to unavoidable shift between imaging and treatment as measured with MOSkin and PTW 9112 detectors. The integration of MOSkin on commercial PTW 9112 surface found to be feasible for rectal dose IVD during cervical HDR ICBT.

Less Than Whole Uterus Irradiation for Locally Advanced Cervical Cancer Maintains Locoregional Control and Decreases Radiation Dose to Bowel.

OBJECTIVE: This study aimed to evaluate whether our institutional standard of less-than-whole-uterus irradiation affects locoregional control in patients with locally advanced cervical cancer. METHODS AND MATERIALS: We retrospectively reviewed 53 patients with stage IB to IVB cervical carcinoma who were treated with image guided intensity modulated radiation therapy and brachytherapy. The entire uterus was not included in the clinical target volume, as per our institutional standard. Dosimetric parameters were obtained, including positron emission tomography gross tumor volume (GTV), uterus volume excluding GTV, proportion of uterus included in the planning target volume (PTV; percentage), volume of overlap between uterus and prescription dose (cm3), minimum and mean dose to the uterus, and bowel V40 and D200cc. Local, regional, and distant failure and death were recorded. RESULTS: The median proportion of the uterus included in the PTV was 66%. With a median follow-up of 44 months, no patient experienced isolated local recurrence, and 2-year locoregional failure was 10.9%. Positron emission tomography GTV correlated significantly with increased chance of any failure (P = .049; 95% confidence interval, 1.000-1.018). Compared with patients who had ≥90% of the uterus included in the PTV (n = 12), patients who had <90% (n = 41) of the uterus included in the PTV had significantly lower bowel V40 (P = .049) and D200cc (P = .006). CONCLUSIONS: Less-than-whole-uterus irradiation for locally advanced cervical cancer does not compromise locoregional control and reduces bowel V40 and D200cc. Further investigation is required to evaluate whether this reduction in bowel dose translates to a clinically significant reduction in bowel toxicity and whether modifications should be made to the recommended definitive cervix intensity modulated radiation therapy volumes.

Cytomorphological features of high-grade intraepithelial neoplasia/carcinoma of the cervix following chemoradiotherapy.

BACKGROUND: Cervicovaginal cytology as a follow-up study in women with a history of a cervical carcinoma treated with chemo-radiotherapy (CRT) plays an important role; however, the cytomorphological characteristics for the diagnosis of high-grade squamous intraepithelial lesions (H-SIL) in post-CRT patients have not been established. The aim of the study is to find the cytomorphological characteristics that support the diagnosis of H-SIL by conventional cytology in these patients. MATERIALS AND METHODS: This is a cross-sectional study from 2009 to 2015, which includes patients with a diagnosis of squamous cell carcinoma treated with CRT, who all have cervix cytology for follow-up and a later biopsy. RESULTS: We identified 82 cases, where the most frequent clinical stage was IIA1 to IIB with 26 cases (61.9%), the most common symptom was transvaginal bleeding (64.29%). The cytological characteristics that were statistically associated with the presence of a positive biopsy were the presence of a hemorrhagic background (45.2% vs. 12.5%, P = .007), high cellularity (45.2% vs. 15%, P < .001), disposition in groups/sheets (69% vs. 22.5%, P < .001), postradiotherapy changes at the background of the smear (73.8 vs. 50%, P < .001) and an increased nuclear/cytoplasmic ratio (100% vs. 22.5%, P < .001). CONCLUSIONS: In patients with CRT, the presence of specific features can help the diagnosis of H-SIL with excellent diagnostic performance.

Kinetics of Intratumoral Immune Cell Activation During Chemoradiation for Cervical Cancer.

PURPOSE: Radiation therapy has direct cytotoxic effects on tumor-infiltrating lymphocytes, but it also has immune stimulatory effects that increase immune cell infiltration. The dynamics of these competing effects on immune cells at the site of the tumor are poorly characterized during chemoradiation treatment (CRT) because of the difficulty of obtaining consecutive tumor biopsies. We used a minimally invasive cervical cytobrushing method to analyze the kinetics of intratumoral immune cell changes in patients with cervical cancer during CRT. METHODS AND MATERIALS: Cervical brushings were obtained from 20 patients with cervical cancer at baseline and during fractionated radiation therapy and cisplatin (weeks 1, 3, and 5). Matching peripheral blood mononuclear cells were obtained from 9 patients at the same time points. Cells were analyzed using multispectral flow cytometry to identify T cell and myeloid cell subsets and their activation status. Changes in immune cell subsets throughout treatment were calculated using matched-pair analysis with Wilcoxon rank sum test. RESULTS: We observed a significant decline in CD3+ total T cells, as well as CD8+ and CD4+ T-cell subsets in the first week of treatment from baseline, followed by variable expansion at weeks 3 and 5. This coincided with higher levels of proliferating CD8+ T cells expressing Ki67 at week 3 of treatment. The percentages of activated CD8+ T cells expressing CD69 continuously increased over the course of treatment, whereas the percentage of activated CD11c+CD11b- dendritic cells was highest during the first week. Many of these changes were not observed in the blood. CONCLUSIONS: Our results identified immune dynamic changes during CRT, indicating that CRT may be immune activating at the site of the tumor. This study also suggests the importance of sequential analyses of the local tumor microenvironment in addition to peripheral blood.

Improving dose delivery by adding interstitial catheters to fixed geometry applicators in high-dose-rate brachytherapy for cervical cancer.

PURPOSE: Image-guided brachytherapy (IGBT) is an essential component of the treatment of locally advanced cervical cancer. Interstitial (IS) catheters are being increasingly used for bulkier tumors. We have retrospectively assessed the dosimetric impact of IS catheters. METHODS AND MATERIALS: All patients who received IGBT for cervical cancer between August 2014 and February 2017 were identified. Clinical and dosimetric data were collected. Patients were grouped into the intracavitary (IC) cohort or the IC and IS implant (IC/IS) cohort. Ten patients who had been treated with IS catheters (IC/IS plan) had their brachytherapy replanned without IS catheters (IC plan). The total D90% received by the high-risk clinical target volume (CTVHR) and the D2cm3 (minimum dose received by the most irradiated 2 cm3) to the bladder, bowel, sigmoid, and rectum were compared. RESULTS: Forty-two patients received IGBT in this period. Seventy-four percent of patients were treated with IS catheters. Sixty-one percent of patients in the IC/IS cohort had CTVHR volumes ≥30 cm3 at Fraction 1 compared to 18% in the IC cohort (p = 0.014). There was no difference in cumulative D90% to CTVHR between the IC/IS cohort and the IC cohort. The replanned brachytherapy showed that the cumulative CTVHRD90% was on average 5.8 Gy higher when IS catheters were used (mean CTVHRD90% 86.1 compared to 80.3 Gy, p < 0.001). The D2cm3 to the organs at risk was not significantly increased. CONCLUSIONS: IS catheters allow the dose to the CTVHR to be escalated significantly without increasing the dose to the bladder, bowel, sigmoid, and rectum in patients with bulky tumors.

Calculation of dose volume parameters and indices in plan evaluation of HDR interstitial brachytherapy by MUPIT in carcinoma cervix.

BACKGROUND: Evaluation of a HDR- interstitial brachytherapy plan is a challenging job. Owing to the complexities and diversity of the normalization and optimization techniques involved, a simple objective assessment of these plans is required. This can improve the radiation dose coverage of the tumour with decreased organ toxicity. AIM: To study and document the various dose volume indices and parameters required to evaluate a HDR interstitial brachytherapy plan by Volume normalization and graphical optimization using MUPIT (Martinez Universal Perineal Interstitial Template) in patients of carcinoma cervix. SETTINGS AND DESIGN: Single arm, retrospective study. METHODS AND MATERIALS: 35 patients of carcinoma cervix who received EBRT and HDR brachytherapy using MUPIT, were selected. The dose prescribed was 4 Gray/Fraction in four fractions (16Gy/4) treated twice daily, at least 6 hours apart. CTV and OARs were delineated on the axial CT image set. Volume normalization and graphical optimization was done for planning. Coverage Index (CI), Dose homogeneity index (DHI), Overdose index (OI), Dose non-uniformity ratio (DNR), Conformity Index (COIN) and dose volume parameters i.e. D2cc, D1cc, D0.1cc of rectum and bladder were evaluated. STATISTICAL ANALYSIS: SPSS version 16 was used. RESULTS AND CONCLUSION: CI was 0.95 ± 1.84 which means 95% of the target received 100% of the prescribed dose. The mean COIN was 0.841 ± 0.06 and DHI was 0.502 ± 0.11. D2cc rectum and bladder was 3.40 ± 0.56 and 2.95 ± 0.62 respectively which was within the tolerance limit of this organs. There should be an optimum balance between these indices for improving the quality of the implant and to yield maximum clinical benefit out of it, keeping the dose to the OARs in limit. Dose optimization should be carefully monitered and an institutional protocol should be devised for the acceptability criteria of these plans.

Cytopathologic evaluation of patients submitted to radiotherapy for uterine cervix cancer.

Cervical cancer is an important public health problem. Pap smear is the leading strategy of screening programs for cervical cancer worldwide. However, delayed diagnosis leads to more aggressive and less effective treatments. Patients with uterine cervix malignancies who are referred for radiotherapy have advanced-stage disease, which results in high rates of locoregional recurrence. The use of radiotherapy as a treatment for cervical cancer causes morphological changes in neoplastic and non-neoplastic epithelial cells, as well as in stromal cells, which make it difficult to diagnose the residual lesion, resulting in a dilemma in cytopathological routine. Based on the difficulties of cytopathologic evaluation for the follow-up of patients treated with radiotherapy for cervical cancer, our objective was to describe the actinic cytopathic effects. Our paper was based on a structured review including the period from June 2015 to April 2016, aiming at an exploratory-descriptive study. Bibliographic investigations were carried out through selection and analysis of articles, list of authors and keywords, selection of new articles focused on the analysis of bibliographic references to previously selected documents, as well as textbooks of recognized merit. The most incident actinic cytopathological alterations as described in the literature are: cellular gigantism, nuclear and cytoplasmic vacuolization, dyskeratosis, bi- and multinucleated (B/M) cells, macro and multiple nucleoli, anisokaryosis, anisonucleolosis and nuclear pyknosis. To date, a protocol has not been established that can precisely differentiate the morphological characteristics between benign cells with actinic effects from recurrent malignant cells on post-radiotherapy smears.

Cytopathologic evaluation of patients submitted to radiotherapy for uterine cervix cancer / Avaliação citopatológica no seguimento de pacientes submetidas à radioterapia por câncer de colo uterino

Summary Cervical cancer is an important public health problem. Pap smear is the leading strategy of screening programs for cervical cancer worldwide. However, delayed diagnosis leads to more aggressive and less effective treatments. Patients with uterine cervix malignancies who are referred for radiotherapy have advanced-stage disease, which results in high rates of locoregional recurrence. The use of radiotherapy as a treatment for cervical cancer causes morphological changes in neoplastic and non-neoplastic epithelial cells, as well as in stromal cells, which make it difficult to diagnose the residual lesion, resulting in a dilemma in cytopathological routine. Based on the difficulties of cytopathologic evaluation for the follow-up of patients treated with radiotherapy for cervical cancer, our objective was to describe the actinic cytopathic effects. Our paper was based on a structured review including the period from June 2015 to April 2016, aiming at an exploratory-descriptive study. Bibliographic investigations were carried out through selection and analysis of articles, list of authors and keywords, selection of new articles focused on the analysis of bibliographic references to previously selected documents, as well as textbooks of recognized merit. The most incident actinic cytopathological alterations as described in the literature are: cellular gigantism, nuclear and cytoplasmic vacuolization, dyskeratosis, bi- and multinucleated (B/M) cells, macro and multiple nucleoli, anisokaryosis, anisonucleolosis and nuclear pyknosis. To date, a protocol has not been established that can precisely differentiate the morphological characteristics between benign cells with actinic effects from recurrent malignant cells on post-radiotherapy smears.

Resumo O câncer de colo uterino configura-se como um importante problema de saúde pública. O teste citopatológico é a principal estratégia de programas de rastreamento dessa neoplasia maligna em todo o mundo. Entretanto, a demora no diagnóstico ocasiona tratamentos mais agressivos e menos efetivos. Pacientes com neoplasia maligna de colo uterino que são encaminhadas para radioterapia apresentam doença em estádios avançados, e esse fato determina altos índices de recidiva locorregional. A utilização da radioterapia como tratamento do câncer do colo uterino provoca alterações morfológicas não só nas células epiteliais neoplásicas e não neoplásicas como também nas células estromais, o que dificulta o diagnóstico da lesão residual e resulta em um dilema na rotina citopatológica. Com base nas dificuldades da avaliação citopatológica do seguimento das pacientes pós-radioterapia, o objetivo deste trabalho foi descrever os efeitos citopáticos actínicos. O trabalho teve como base uma revisão estruturada no período de junho de 2015 a abril de 2016, visando a um estudo exploratório-descritivo. As investigações bibliográficas foram realizadas por meio de seleção e análise dos artigos, lista de autores e palavras-chave; seleção de novos artigos focada na análise de referências bibliográficas dos documentos previamente selecionados e livros-texto de relevância conceitual. As alterações citopatológicas actínicas mais incidentes descritas na literatura são: gigantismo celular, vacuolização nuclear e citoplasmática, disceratose, bi e multinucleações, macro e múltiplos nucléolos, anisocariose, anisonucleolose e picnose nuclear. Até o momento, não se conseguiu estabelecer um protocolo que possa diferenciar precisamente as características morfológicas entre células benignas com efeitos actínicos das células malignas recidivantes em esfregaços pós-radioterapia.

Variation in uterus position prior to brachytherapy of the cervix: A case report.

Rationale: brachytherapy is administered in the treatment of patients with locally advanced cervical cancer following chemoradiotherapy. Lack of local anatomy evaluation prior to this procedure might lead to the selection of an inappropriate brachytherapy applicator, increasing the risk of side effects (e.g. uterus perforation, painful procedure ...). Objective: To assess the movement of the uterus and cervix prior to brachytherapy in patients with gynecological cancer, in order to select the proper type of brachytherapy applicator. Also we wanted to promote the replacement of the plain X-ray brachytherapy with the image-guided procedure. Methods and results: We presented the case of a 41-year-old female diagnosed with a biopsy that was proven cervical cancer stage IIIB. At diagnosis, the imaging studies identified an anteverted uterus. The patient underwent preoperative chemoradiotherapy. Prior to brachytherapy, the patient underwent a pelvic magnetic resonance imaging (MRI), which identified a displacement of the uterus in the retroverted position. Discussion: A great variety of brachytherapy applicators is available nowadays. Major changes in uterus position and lack of evaluation prior to brachytherapy might lead to a higher rate of incidents during this procedure. Also, by using orthogonal simulation and bidimensional (2D) treatment planning, brachytherapy would undoubtedly fail to treat the remaining tumoral tissue. This is the reason why we proposed the implementation of a prior imaging of the uterus and computed tomography (CT)/ MRI-based simulation in the brachytherapy procedure. Abbreviations: MRI = magnetic resonance imaging, CT = computed tomography, CTV = clinical target volume, DVH = dose-volume histogram, EBRT = external beam radiotherapy, GTV = gross tumor volume, Gy = Gray (unit), ICRU = International Commission of Radiation Units, IGRT = image guided radiotherapy, IM = internal margin, IMRT = image modulated radiotherapy, ITV = internal target volume, MRI = magnetic resonance imaging, OAR = organs at risk, PTV = planning target volume, QUANTEC = Quantitative Analyses of Normal Tissue Effects in the Clinic.

Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System.

PURPOSE: The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. METHODS: The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. RESULTS: In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions. CONCLUSIONS: The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

High-risk CTV delineation for cervix brachytherapy: Application of GEC-ESTRO guidelines in Australia and New Zealand.

INTRODUCTION: Image-based brachytherapy for cervical cancer using MRI has been implemented in Australia and New Zealand. The aims of this study were to measure variability in High-risk CTV (HR-CTV) delineation and evaluate dosimetric consequences of this. METHODS: Nine radiation oncologists, one radiation therapist and two radiologists contoured HR-CTV on 3T MRI datasets from ten consecutive patients undergoing cervical brachytherapy at a single institution. Contour comparisons were performed using the Dice Similarity Coefficient (DSC) and Mean Absolute Surface Distance (MASD). Two reference contours were created for brachytherapy planning: a Simultaneous Truth and Performance Level Estimation (STAPLE) and a consensus contour (CONSENSUS). Optimized plans (8 Gy) for both these contours were applied to individual participant's contours to assess D90 and D100 coverage of HR CTV. To compare variability in dosimetry, relative standard deviation (rSD) was calculated. RESULTS: Good concordance (mean DSC≥0.7, MASD≤5 mm) was achieved in 8/10 cases when compared to the STAPLE reference and 6/10 cases when compared to the CONSENSUS reference. Greatest variation was visually seen in the cranio-caudal direction. The average mean rSD across all patients was 27% and 34% for the STAPLE HR-CTV D90 and D100, respectively, and 28% and 35% for the CONSENSUS HR-CTV D90 and D100. Delineation uncertainty resulted in an average dosimetric uncertainty of ±1.5-1.6 Gy per fraction based on an 8 Gy prescribed fraction. CONCLUSIONS: Delineation of HR-CTV for cervical cancer brachytherapy was consistent amongst observers, suggesting similar interpretation of GEC-ESTRO guidelines. Despite the good concordance, there was dosimetric variation noted, which could be clinically significant.

Simultaneous integrated boost (SIB) of the parametrium and cervix in radiotherapy for uterine cervical carcinoma: a dosimetric study using a new alternative approach.

OBJECTIVE: To compare the dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous integrated boost (SIB) technique with that of the traditional midline block (MB) technique for boosting the parametrium in patients with cervical cancer. METHODS: Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB) and IMRT followed by the MB technique (IMRT-MB) were generated for each of the 10 patients with cervical cancer. For the SIB plans, 45-Gy and 50-Gy dose levels in 25 equal fractions were set for the pelvis planning target volume 45 (PTV45) and the parametrial boost volume (PTV50), respectively. For the IMRT-MB plans, the parametrium was sequentially boosted with the MB technique (5.4 Gy in three fractions) after pelvic IMRT (PTV45). RESULTS: Volume receiving 100% of the prescribed dose or more coverage of the PTV50 was significantly better for VMAT-SIB and IMRT-SIB than that for IMRT-MB (99.08 and 99.31% compared with 91.79%, respectively; p < 0.05). VMAT-SIB and IMRT-SIB both generated significantly greater doses to the organs at risk (OARs) except for the volume receiving 50 Gy or more doses, which were significantly lower for the bladder and bowel. Comparable results were achieved with VMAT-SIB and IMRT-SIB. CONCLUSION: The VMAT-SIB and IMRT-SIB techniques are promising in terms of dose distributions and tumour coverage, although these approaches might result in slightly higher doses of radiation to the OARs. Advances in knowledge: This is the first study to examine the feasibility of the SIB technique using IMRT or VMAT to boost the parametrium. The techniques dosimetrically produced better target coverage but resulted in slightly higher doses to the OARs.

Occult invasive cervical cancer after simple hysterectomy: a multi-center retrospective study of 89 cases.

BACKGROUND: Occult invasive cervical cancer (OICC) is sometimes incidentally found in surgical specimens after a simple hysterectomy (SH). This study was aimed at identifying a subset of patients with OICC who have a favorable prognosis. This patient group may not require adjuvant radiotherapy and other procedures. METHODS: The medical records of women in whom OICC was detected after an inadvertent SH were retrospectively reviewed. The relevant data, including clinicopathological characteristics, treatment and clinical outcome were evaluated. The primary and secondary endpoints were overall survival (OS) and relapse-free survival (RFS), respectively. RESULTS: Eighty-nine patients who met the inclusion criteria were included for analysis, and the risk of OICC was found to be 1.9 %. Finding an invasive cancer in a hysterectomy specimen after a conization procedure that shows positive margins was the most common reason (41.6 %) for the performance of inadvertent SH. In the univariate analysis, a tumor width > 20 mm, deep stromal invasion, and lymph node metastasis (LNM) were adversely associated with relapse (P < 0.001, < 0.001, and = 0.001, respectively) and survival (P = 0.003, 0.004, and 0.027, respectively), although these parameters were not independently associated with patient prognoses in the multivariate analysis. In patients with a tumor width ≤ 20 mm and superficial stromal invasion in the observation subgroup, the 5-year RFS and 5-year OS were both 100 %, whereas they were 57.1 % and 66.7 %, respectively, in patients with a tumor size > 20 mm and deep stromal invasion in the radiotherapy or chemotherapy subgroup (P < 0.001, and = 0.008, respectively). CONCLUSIONS: Simple observation after a lymphadenectomy procedure may be feasible in OICC patients with a tumor width ≤ 20 mm, superficial stromal invasion, a negative section margin in hysterectomy specimens, and no LNM.