Nalee Kim

Radiotherapy in recurrent ovarian cancer: updated results of involved-field radiation therapy

This study aimed to update the possible clinical benefits of radiation therapy in recurrent ovarian cancer. The medical records of 495 patients with recurrent ovarian cancer after initially undergoing maximal cytoreductive surgery and adjuvant platinum-based chemotherapy based on the pathologic stage between January 2010 and December 2020 were analyzed: 309 and 186 patients were treated without and with involved-field radiation therapy, respectively. Involved-field radiation therapy is defined as radiation therapy only to the areas of the body involved by tumor. The prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). Overall survival was compared between patients treated with and without involved-field radiation therapy. The favorable group was defined as patients who satisfied at least four of the following factors: good performance, no ascites, normal CA-125, platinum-sensitive tumor, and nodal recurrence. The median age of the patients was 56 years (range 49-63) and median time to recurrence was 11.1 months (range 6.1-15.5). 217 patients (43.8%) were treated at a single site. Radiation therapy, performance status, CA-125, platinum sensitivity, residual disease, and ascites were all significant prognostic factors. The 3-year overall survival of all patients, patients treated without radiation therapy, and patients treated with radiation therapy was 54.0%, 44.8%, and 69.3%, respectively. Radiation therapy was associated with higher overall survival rates in the unfavorable and favorable patient groups. Patient characteristics showed higher rates of normal CA-125, lymph node metastasis only, lower platinum sensitivity, and higher rates of ascites in the radiation therapy group. After propensity score matching, the radiation therapy group showed superior overall survival to the non-radiation therapy group. Normal CA-125, good performance status, and platinum sensitivity were associated with a good prognosis in patients treated with radiation therapy. Our study showed that higher overall survival was observed in patients treated with radiation therapy in recurrent ovarian cancer.

Use of bevacizumab before or after radiotherapy increases the risk of fistula formation in patients with cervical cancer

Several reports have documented the risk of fistula formation after bevacizumab in patients previously treated with radiation therapy. The aim of this study was to investigate the risk of fistula formation with bevacizumab and radiotherapy compared with radiotherapy alone. We retrospectively analyzed patients with stage I-IV cervical cancer between January 2013 and December 2018. Patients who had a history of pelvic radiotherapy, who were treated with intracavitary brachytherapy alone, received radiotherapy at another hospital, received concurrent bevacizumab and radiotherapy, or had missing follow-up data or a short follow-up period (<6 months) were excluded. The fistula rates were compared between the groups using the Cox proportional hazards model and propensity score analyses. A total of 302 patients were included in the study: 249 patients were treated with definitive or adjuvant radiotherapy, and 53 patients were treated with radiotherapy before or after bevacizumab. With a median follow-up of 35.9 (IQR 22.8-53.5) months, the 3 year cumulative fistula incidence rate was significantly higher in the radiotherapy + bevacizumab group than in the radiotherapy group (27.0% vs 3.0%, p<0.001). Bevacizumab administration was significantly associated with fistula formation in the multivariable adjusted model (HR 4.76, 95% CI 1.71 to 13.23) and three propensity score adjusted model (all p<0.05). Biologically equivalent dose in 2 Gy fractions for 2 cc of the rectum more than 76 Gy was also associated with fistula formation (HR 4.30, 95% CI 1.52 to 12.18). Additionally, a 10 month interval between radiotherapy and bevacizumab reduced the incidence of fistula formation in the radiotherapy + bevacizumab group (p=0.032). In patients with cervical cancer treated with pelvic radiotherapy, the addition of bevacizumab substantially increased the risk of fistula formation. Physicians should perform pelvic radiotherapy in combination with bevacizumab with caution; moreover, close monitoring for fistula formation is warranted in these patients.

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer

Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0-1+) (n=120 patients) and moderate/strong (2-3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. Patients with KLK5 2-3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0-1+. With a median follow-up of 60.8 (interquartile range, 47.5-77.9) months, patients with KLK5 2-3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0-1+ group) and 59.4% (vs. 72.8% in the KLK5 0-1+ group), respectively (all p<0.05). KLK5 2-3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

Significance of serum CA125 level in surgically resected cervical adenocarcinoma with adverse features

Unlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features. A total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model. Using a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7-97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003). In this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.

Patterns of definitive radiotherapy practice for cervical cancer in South Korea: a survey endorsed by the Korean Radiation Oncology Group (KROG 20-06)

The Korean Radiation Oncology Group conducted a nationwide questionnaire survey to evaluate the patterns of clinical practice for patients with cervical cancer receiving definitive radiation therapy (RT) in South Korea. Practicing radiation oncologists from 93 centers in South Korea were administered a questionnaire survey via e-mail. The survey focused on demographic characteristics, diagnostic evaluation, indications for definitive RT, RT techniques, RT field and dose prescription, lymph node (LN) boost RT, brachytherapy, and chemotherapy. The response rate was 62.4% (58/93 institutions). Of the 2,134 patients treated at the radiation oncology department in 2019, 48.8% underwent definitive RT. The selection of patients for definitive concurrent chemoradiation therapy and RT field, and RT dose prescription varied greatly. The upper border of the pelvis was commonly used as the bony landmark for external beam RT (81%-88% of respondents). Most (96.6%) centers performed LN boost RT with median total doses of 59 Gy and 59.2 Gy for pelvic and retroperitoneal LN, respectively. With 50% of the centers offering brachytherapy, image-guided brachytherapy and volume-based prescription were applied in 48.3% and 37.9%, respectively. Upfront concurrent chemoradiation therapy with varying prescription doses was considered by 60.4% respondents in cases of supraclavicular LN metastasis. Most differences were noted in the indications for treatment, RT field, and prescription dose. This finding can serve as a reference for establishing practical RT guidelines for the management of locally advanced cervical cancer.

Adjuvant radiotherapy for cervical cancer in South Korea: a radiation oncology survey of the Korean Radiation Oncology Group (KROG 20-06)

Abstract Objective Radiation therapy plays an important role in adjuvant treatment for surgically treated cervical cancer with adverse pathological findings. This was the first study to evaluate current practices of adjuvant radiation therapy among centres affiliated with the Korean Radiation Oncology Group. Methods A survey containing specific questions on the demographics in 2019, indications of adjuvant treatment, radiation therapy field, prescription radiation therapy dose, boost radiation therapy and chemotherapy was sent out by e-mail to 93 centres. Results The overall response rate was 62.4%. Regarding radiation therapy techniques, intensity-modulated radiation therapy was adopted in most institutions (41/58, 70.7%). Various risk group criteria were selected for adjuvant radiation therapy and concurrent chemoradiation therapy. One or two risk factors among tumour size, depth of invasion and lymphovascular invasion were considered for adjuvant radiation therapy by 20.7 and 60.3% of the respondents, respectively. The following criteria for concurrent chemoradiation therapy were considered by 60.3% of the respondents: parametrial extension, positive resection margin or lymph node metastasis. Various upper borders were preferred for pelvic radiation therapy by the institutions, and a total dose of 50.4 Gy in 28 fractions was the most prescribed dose scheme (37/58, 63.8%). Lymph node bed boost radiation therapy and vaginal cuff brachytherapy were considered for selected patients by 22.4% (13/58) and 60.3% (35/58) of the institutions. Conclusion This survey demonstrated the practice patterns of adjuvant treatment that are prevalent in the field of radiation oncology among members of the Korean Radiation Oncology Group. These findings warrant further consensus on radiation therapy guidelines in the context of adjuvant treatment for cervical cancer.

Clinical outcomes after positron emission tomography/computed tomography‐based image‐guided brachytherapy for cervical cancer

AbstractIntroductionAlthough positron‐emission tomography (PET) plays an integral role in cervix cancer diagnosis, there are limited data on PET‐based image‐guided brachytherapy (IGBT). We aimed to report the long‐term outcomes of PET‐based IGBT.MethodsWe reviewed 151 patients treated with definitive radiotherapy (RT), including PET‐based IGBT between 2009 and 2018. After median 45 Gy of external beam RT with the four‐field technique, a median 24 Gy of high‐dose‐rate iridium‐192 IGBT was delivered in six fractions with Fletcher‐Suit tandem and ovoids. All patients underwent 18F‐fluorodeoxyglucose‐PET/computed tomography planning with a brachytherapy applicator. Multivariable analysis of local control (LC) was performed using Cox regression analysis.ResultsThe median high‐risk clinical target volume (HRCTV) and HRCTV D90% were 51.8 (interquartile range [IQR] 35.9–79.4) cm3 and 77.7 (IQR 74.7–81.2) Gy, respectively. With a median follow‐up of 57 (IQR 24.3–81.4) months, the 5‐year LC rate was 89.2%. HRCTV ≥72 cm3 was associated with inferior LC (hazard ratio, 3.72, p = .017) after multivariable analysis: the 5‐year LC rates were 94.0% and 77.9% for HRCTVs ≥72 and &lt; 72 cm3, respectively (p = .002). The impact of HRCTV D90% ≥70 Gy on LC was significant in patients with an HRCTV ≥72 cm3 compared to that in those with HRCTV &lt; 72 cm3. Patients with adeno/adenosquamous carcinoma demonstrated inferior LC in both groups. There were 13 (8.6%) and 11 (7.3%) patients with acute and late severe toxicities after RT.ConclusionPET‐based IGBT leads to favorable LC, and HRCTV ≥72 cm3 requires further dose escalation to improve outcomes.