Radiotherapy For Uterine Cervical Cancer Research Articles

Secondary cancers after carbon-ion radiotherapy and photon beam radiotherapy for uterine cervical cancer: Acomparative study.

BackgroundThere are limited studies on the risk of secondary cancers after carbon‐ion radiotherapy (CIRT). We assessed the incidence of secondary cancers in patients treated with CIRT for cervical cancer. We also evaluated the incidence of secondary cancers in patients who received standard photon radiotherapy (RT) throughout the same period.MethodsThis retrospective study included patients with cervical cancer who underwent curative RT at our hospital. All cancers discovered for the first time after RT were classified as secondary cancers. To compare the risk of secondary cancers among cervical cancer survivors to the general population, standardized incidence ratios (SIRs) were calculated.ResultsThe analysis included a total of 197 and 417 patients in the CIRT and photon RT groups, respectively. The total person‐years during the observation period were 1052.4 in the CIRT group and 2481.5 in the photon RT group. The SIR for all secondary cancers was 1.1 (95% confidence interval [CI], 0.6–2.1) in the CIRT group and 1.4 (95% CI, 1.0–2.1) in the photon RT group. The 10‐year cumulative incidence of all secondary cancers was 9.5% (95% CI, 4.0–21.5) in the CIRT group and 9.4% (95% CI, 6.2–14.1) in the photon RT group. The CIRT and photon RT groups were not significantly different in incidence (p = 0.268).ConclusionsThe incidence of secondary cancers after CIRT for cervical cancer was similar to that after photon RT. Validation of our findings after long‐term observation is warranted.

Clinical impact of sarcopenia in patients with uterine cervical cancer treated with radiotherapy

Objective: Though sarcopenia is known to be associated with worse prognosis in various tumors, studies regarding the significance of sarcopenia in uterine cervical cancer are uncommon. We investigated the clinical impact of sarcopenia in patients with uterine cervical cancer treated with radiotherapy (RT). Methods: Among 104 patients who received RT for uterine cervical cancer between 2011 and 2018, 58 patients treated with a definitive or adjuvant aim were included in this study. Sarcopenia was determined by measuring the skeletal muscle area using computed tomography that was performed for RT planning. Results: Among the 58 patients, 30 patients (51.7%) had sarcopenia and 20 patients (66.7%) with sarcopenia had a normal body mass index (BMI). The median age of patients was 55.5 years. There was no linear relationship between age and prevalence of sarcopenia. During the median follow-up period of 35 months, 3 patients died and 11 patients had disease recurrence or progression. Sarcopenia was associated with a worse progression-free survival (PFS; HR 12.301, 95% CI 2.243–67.450, p = 0.004). The 2-year PFS rates of patients with and without sarcopenia were 66.3% and 92.3%, respectively (p = 0.008). Conclusions: Sarcopenia was observed in approximately half of the patients who received RT for cervical cancer, including patients with a normal BMI. Sarcopenia was associated with a worse PFS, and treatment interruption or discontinuation was more frequent among patients with sarcopenia. Evaluation of skeletal muscle mass and support to reduce skeletal muscle loss could be useful to optimize treatment and achieve better PFS.

Predictive factors of posttreatment fracture by definitive radiotherapy for uterine cervical cancer

PurposeFractures are known to shorten life expectancy and worsen the quality of life. The risk of fractures after radiation therapy in cervical cancer patients is known to be multifactorial. In this study, we examined risk factors for fractures in cervical cancer patients, especially by evaluating bone densities and DVH parameters for fractured bones.Materials and MethodsFor 42 patients, clinical characteristics, pretreatment CT bone densities, and radiation dose were compared between patients with and without fractures.ResultsPosttreatment fractures occurred in 25 bones among ten patients. Pretreatment CT bone densities were significantly lower in patients with fractures (P < 0.05–0.01 across sites, except for the ilium and the ischium). Although DVH parameters were also significantly associated with fractures in univariate analysis, only CT densities were significantly associated with fractures in multivariate analysis.ConclusionPretreatment CT densities of spinal and pelvic bones, which may reflect osteoporosis, have a significant impact on the risk for posttreatment fractures.

Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy

DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9%, P=0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3%, P=0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P=0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5%, P=0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.

Walking Disability in Patients with Pelvic Insufficiency Fracture after Radiotherapy for Uterine Cervical Cancer.

Radiotherapy is an essential component of curative or palliative therapy for patients with uterine cervical cancer. Although advances in radiotherapy have led to longer survival, survivors may consequently be at risk of pelvic insufficiency fracture (PIF). We retrospectively reviewed medical records and clinical outcomes to assess the impact of PIF on walking disability. Between January 2002 and December 2009, 145 uterine cancer patients treated with radiotherapy in our hospital were reviewed. Among these, 15 patients (10.3%) were diagnosed with PIF. The types of fractures were identified according to the AO/OTA classification system. Medical records were examined to establish the time to first diagnosis of PIF, the type of fracture, and clinical outcomes. Disability was assessed using Barthel index mobility scores. The median time to PIF detection was 16 months. Of the 15 patients with PIF, 14 had type B fractures (7 cases of B2 and 7 cases of B3) and 1 had a type C fracture. Among 11 patients with pelvic pain, 6 achieved pain control but 5 patients with bilateral lesions in the posterior arch or lateral compression of the sacrum developed pain that finally resulted in walking disability and a lower performance status. PIF causes severe motor disturbance in patients with unstable fracture types. Routine imaging checkups were useful during the 5 years after completion of radiotherapy; in nine patients the fracture progressed for longer than 1 year. In cancer rehabilitation for PIF patients, continuous assessment is essential for predicting walking disability.

Early Outcomes and Dose-Volume Parameters for CT-Based Treatment Planning in Brachytherapy for Cervical Cancer With Severe Vaginal Invasion or Vaginal Cancer

DIR (p < 0.005). Similarly, the value between reference CT and CT of ICBT was significantly ameliorated from 0.60 to 0.87 (p < 0.005). Simple rectal D2cc ranged from 70.5Gy to 88.5, and DIR-based rectal D2cc from 65.5Gy to 87.4Gy. Ten of 14 patients (71%) had higher simple rectal D2cc than DIR-based rectal D2cc, and the mean dose using simple rectal D2cc was 1.3 Gy higher than that using DIR-based rectal D2cc. Conclusions: DIR method may allow us to track more accurate total dose from multiple treatment planning CT of radical radiotherapy for uterine cervical cancer. The clinical impact of difference between simple rectal D2cc and DIR-based rectal D2cc warrants further investigation.

Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.

Short-course palliative radiotherapy for uterine cervical cancer

PurposeThe purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer.Materials and MethodsSeventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions.ResultsThe median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity.ConclusionShort-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.

Bone Injury after Definitive Radiotherapy for Uterine Cervical Cancer: Retrospective Analysis of Risk Factors

Bone Injury after Definitive Radiotherapy for Uterine Cervical Cancer: Retrospective Analysis of Risk Factors

Insufficiency Fractures after Pelvic Radiotherapy for Uterine Cervical Cancer: An Analysis of Subjects in a Prospective Multi-institutional Trial, and Cooperative Study of Japan Radiation Oncology Group (JAROG) and Japanese Radiation Oncology Study Group (JROSG)

To investigate the pelvic insufficiency fractures (IF) post definitive pelvic radiotherapy for early stage uterine cervical cancer, we analyzed the subject in a prospective multi-institutional study (JAROG0401/ JROSG04-2).

A Consensus-based Guideline Defining the Clinical Target Volume for Pelvic Lymph Nodes in External Beam Radiotherapy for Uterine Cervical Cancer

To develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field.

Management of Lower Urinary Tract Dysfunction After Radical Hysterectomy With or Without Radiotherapy for Uterine Cervical Cancer

Urinary dysfunction is a common long-term sequela after radical hysterectomy (RH). The aims of this study were to investigate the characteristics and treatment response of lower urinary tract dysfunction (LUTD) after RH with or without adjuvant radiotherapy (RT) for uterine cervical cancer. We analyzed retrospectively 49 patients who developed LUTD after RH with (n = 16) or without (n = 33) RT for stage IB or IIA uterine cervical cancer. The mean interval between RH and first visit for urological management of LUTD was significantly shorter in the RH+RT (5.9 +/- 4.5 years) than the RH (11.3 +/- 9.5; p < 0.05) group. Combined therapy also resulted in a smaller bladder capacity and poorer bladder compliance. Further urological management was given to 29 patients, including a pubovaginal sling procedure in seven, urethral injection of botulinum toxin A in 13, transurethral incision of the bladder neck in three, and augmentation enterocystoplasty in six. Among the patients who received active urological management, 88.9% were satisfied with the outcome. Patients treated with RH+RT are likely to have a worse bladder condition and require urological intervention sooner than those who receive RH alone. Active urological management of LUTD in these patients leads to satisfactory improvements in symptoms of difficult urination and urinary incontinence.

The Effect of Cyclooxygenase-2 Expression on Tumor Volume Response in Patients Treated with Radiotherapy for Uterine Cervical Cancer

We investigated the correlation between Cyclooxygenase-2 (COX-2) expression and the tumor response in patients with cervical cancer that were treated with curative radiotherapy (RT). Fifty-seven patients with squamous cell carcinoma were treated with concurrent radiochemotherapy (CRCT, n=29) or RT alone (n=28). The response of each patient was evaluated by three serial Magnetic Resonance Imaging examinations: before the start of RT, at four weeks after the start of RT (mid-RT) and at four weeks after the completion of RT (post-RT). Forty-three patients had positive COX-2 expression. The COX-2 negative patients achieved a higher rate of complete response (CR) at mid-RT than did the COX-2 positive patients (28.6% vs. 7.0%, P=0.054), but not at post-RT (64.3% vs. 69.8%). The initial tumor volume was a significant predictor of CR at mid-RT (P=0.003) and post-RT (P=0.004). The multivariate analysis showed that the initial tumor volume (at mid-RT and post-RT) and CRCT (at post-RT) were significant predictors of CR; however, the COX-2 expression was not. In conclusion, the COX-2 expression status has no significant correlation with the tumor response. Further studies on the changes in COX-2 expression levels during RT may be helpful for determination of its role in the tumor response to treatment and patient prognosis.

Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer

BackgroundRadiotherapy can be used to treat all stages of cervical cancer. For improving local control via radiotherapy, it is important to use additional antitumor agents. Aminopeptidase N (APN)/CD13, a 150-kDa metalloproteinase, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression in several human malignancies.MethodsWe investigated whether the suppression of APN/CD13 using Ubenimex, an inhibitor of APN/CD13 activity, may affect tumor radiosensitivity in cervical cancer cells both in vitro and in vivo. Cell surface APN/CD13 activity in HeLa cells was calculated using alanine-p-nitroanilido as a substrate. For colony formation assays, single-dose radiation and/or Ubenimex were administered to each dish of HeLa cells, and these dishes were cultured for 14 days. Molecular changes of apoptosis were determined by Western blot. Apoptosis was evaluated by Annexin-V PI staining (flow cytometry analysis) and the Tunel method. Moreover, we investigated the effect of combining Ubenimex and low-dose radiation on tumor growth using nude mice.ResultsWe demonstrated that Ubenimex enhanced the effectiveness of radiotherapy, acting as a radiosensitizer both in vitro and in vivo. In colony formation assays, a significant decline in clonogenic survival was observed in Ubenimex-treated cells. Mice treated with a combination of radiation and Ubenimex showed a significant prolongation of the tumor-doubling time compared with the control, Ubenimex, or radiation-alone groups. We also showed that ubenimex enhanced radiation-induced apoptosis in vitro and in vivo.ConclusionAlthough further studies are needed, this report suggests that Ubeniemx acts as a radiosensitizer in cervical cancer treatment, and that the inhibition of APN/CD13 activity may represent a new approach for improving the therapeutic efficacy of radiotherapy for uterine cervical cancer.

2345: Correlation Between Cyclooxygenase-2 Expression and Tumor Volume Response in Patients Treated With Radiotherapy for Uterine Cervical Cancer

2345: Correlation Between Cyclooxygenase-2 Expression and Tumor Volume Response in Patients Treated With Radiotherapy for Uterine Cervical Cancer

Interfractional dose variation during intensity-modulated radiation therapy for cervical cancer assessed by weekly CT evaluation

To investigate the interfractional dose variation of a small-bowel displacement system (SBDS)-assisted intensity-modulated radiation therapy (IMRT) for the treatment of cervical cancer. Four computed tomography (CT) scans were carried out in 10 patients who received radiotherapy for uterine cervical cancer. The initial CT was taken by use of the SBDS, before the beginning of radiotherapy, and 3 additional CT scans with the SBDS were done in subsequent weeks. IMRT was planned by use of the initial CT, and the subsequent images were fused with the initial CT set. Dose-volume histogram (DVH) changes of the targets (planning target volume [PTV] = clinical target volume [CTV] + 1.5 cm) and of the critical organs were evaluated after obtaining the volumes of each organ on 4 CT sets. No significant differences were found in PTV volumes. Changes on the DVH of the CTVs were not significant, whereas DVH changes of the PTVs at 40% to 100% of the prescription dose level were significant (V(90%); 2nd week: p = 0.0091, 3rd week: p = 0.0029, 4th week: p = 0.0050). The changes in the small-bowel volume included in the treatment field were significant. These were 119.5 cm3 (range, 26.9-251.0 cm3), 126 cm3 (range, 38.3-336 cm3), 161.9 cm3 (range, 37.7-294.6 cm3), and 149.1 cm3 (range, 38.6-277.8 cm3) at the 1st, 2nd, 3rd, and 4th weeks, respectively, and were significantly correlated with the DVH change in the small bowel, which were significant at the 3rd (V80%; p = 0.0230) and 4th (V80%; p = 0.0263) weeks. The bladder-volume change correlated to the large volume change (>20%) of the small-bowel volume. Significant DVH differences for the small bowel can result because of interfractional position variations, whereas the DVH differences of the CTV were not significant. Strict bladder-filling control and an accurate margin for the PTV, as well as image-guided position verification, are important to achieve the goal of IMRT.

Radiotherapy for Uterine Cervical Cancer: Results of the 1995-1997 Patterns of Care Process Survey in Japan

The aim of this study is to establish Japanese national practice patterns for uterine cervical cancer patients who received radiotherapy without surgery. The Japanese Patterns of Care Study (JPCS) conducted a national survey of 73 institutions using two-stage cluster sampling, and collected specific information on 591 patients with uterine cervical cancer treated by radiotherapy without planned surgery between 1995 and 1997. The median age of the patients was 70 years. Karnofsky performance status (KPS) was >/=90 for 37%. Most patients (95%) had histology of squamous cell carcinoma. Ten percent were stage I, 29% stage II, 48% stage III and 13% stage IVA. Photon beams of 10-14 MV were the most used for external beam radiotherapy (EBRT). The beam energy utilized varied significantly by institution strata. Midline block was used in approximately 70% of institutions. Intracavitary brachytherapy (ICBT) was performed in 77%. Institution strata correlated significantly with the ICBT application. The majority of patients (89%) were treated with high-dose-rate (HDR) ICBT. The median single point A dose of HDR-ICBT was 600 cGy. The median summated point A dose from EBRT and HDR-ICBT was 5800 cGy (range: 1196-8600). The median overall treatment time including ICBT was 49 days. Twenty-four percent of the patients received chemotherapy. Concurrent chemoradiation was performed in 5%. The JPCS established the Japanese national practice patterns of care for uterine cervical cancer patients treated with radiotherapy without planned surgery between 1995 and 1997. This survey demonstrated that the institutional strata significantly affected several practice patterns.

Radiation therapy of cervical cancer: Current status in Korea and recent developments

Brachytherapy is an essential part of the radiotherapy for uterine cervical cancer. Since 1979, high dose rate (HDR) brachytherapy has been used for the treatment of uterine cervical cancer in Korea; the number of institutions employing HDR has been increasing. At 40 radiation oncology departments out of 53 in Korea, HDR brachytherapy was practiced in 2004. Approximately in 1,000 of patients, brachytherapy was done annually and among these, HDR proportions were 75-80%. In Korea, treatment results for HDR are comparable with the low dose rate (LDR) system series and appear to be a safe and effective alternative to LDR for the treatment of cervical carcinoma. The studies from the major centers report the five-year survival rate of cervical cancer as, 78-86% for Stage I, 68-85% for stage II, and 38-56% for Stage III. In conclusion, HDR intracavitary radiotherapy is increasingly practiced in Korea and an effective treatment modality for cervical cancer. To determine the optimum radiation dose and fractionation schedule, a nation-wide prospective study is necessary in Korea. Recently a three-dimensional conformal radiotherapy (3DCRT) or an intensity-modulated radiotherapy (IMRT), which allow for a high degree of conformity to the target volume have been used for the uterine cervical cancer. Several studies have reported the superiority of IMRT, over the conventional technique, in reducing the small bowel dose. The author will introduce the small bowel displacement system (SBDS)-assisted IMRT for cervical cancer patients. Positional changes of the uterus during radiotherapy, which can degrade the accuracy of 3DCRT and IMRT, will be discussed.

Postoperative radiotherapy for uterine cervical cancer: results of the 1995-1997 patterns of care process survey in Japan.

To determine the average national practice of postoperative radiotherapy for uterine cervical cancer in Japan. The Japanese Patterns of Care Study (PCS) reviewed the process of care employed for 455 uterine cervical cancer patients who were treated with surgery followed by postoperative radiotherapy (RT) during 1995-1997. Cases with missing data were excluded from calculations of percentage and significance for each of the surveyed items. According to FIGO stages, 198 patients (45%) were in stage I, 52 patients (12%) were in stage IIA, 146 patients (33%) were in stage IIB and 46 patients (10%) were in stage III/IVA. The most common surgical procedure among the patients was radical hysterectomy (73%). Three hundred and seventy patients (82%) were treated with external beam RT (ERT) alone, and 74 patients (17%) were treated with a combination of ERT and intracavitary RT (ICRT). A midline block was used for the pelvic field in 63 patients (14%). Only seven patients (2%) were treated with extended field ERT. Pelvic ERT was most often performed using AP-PA opposed fields for 431 patients (97%). A majority of the patients (312 patients, 70%) were treated with a total dose of 45.0-50.4 Gy for ERT. Chemotherapy (CT) was administered to 178 patients (40%), neoadjuvant preoperative CT was administered to 80 patients (22%) and concurrent CT with postoperative RT was administered to 29 patients (8%). This PCS established the national practice average of postoperative RT for uterine cervical cancer. Follow-up studies need to be conducted to determine whether the observed differences in treatment processes affect outcomes.

Clinicopathologic characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer

This study was designed to clarify the characteristics of large bowel cancer developing after radiotherapy for uterine cervical cancer. A retrospective chart review was performed. The latent period was a mean of 20.5 years. The most common site was in the rectum (16/32). Mucin-producing carcinoma was observed in 53.1 percent, with an especially high rate of 75 percent in the rectum. Histologic radiation damage was also demonstrated at a high rate of 64.3 percent. It was difficult to judge from clinicopathologic findings whether large bowel cancer developed with relation to radiation effect. We emphasize, however, that the characteristics are different from ordinary large bowel cancer. Particular consideration should be given to the high incidence of mucin-producing carcinoma.