Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD).

BACKGROUND: Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer. PRIMARY OBJECTIVE: The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment. STUDY HYPOTHESIS: Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response. TRIAL DESIGN: All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months. MAJOR INCLUSION/EXCLUSION CRITERIA: The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal. PRIMARY ENDPOINT: The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis. SAMPLE SIZE: Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023. TRIAL REGISTRATION: NCT04593381.

Stereotactic body radiotherapy in oligometastatic cervical cancer (MITO-RT2/RAD study): a collaboration of MITO, AIRO GYN, and MaNGO groups.

OBJECTIVE: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer. METHODS: A standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a 'per lesion' basis. The secondary end points were progression-free survival and overall survival, as well as toxicity. RESULTS: A total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10-60), in five fractions (range 1-10), with a median dose/fraction of 7 Gy (range 4-26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a 'per lesion' basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events. CONCLUSION: Our analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting.

Image-guided brachytherapy in cervical cancer including fractionation.

Image-guided brachytherapy in cervical cancer has been developed to be a feasible and very efficient component of the treatment of locally advanced cervical cancer in addition to concurrent chemoradiation treatment. This technique allows effective dose coverage of the target while sparing the organs at risk through adjustment of the implants (intracavitary and interstitial needles) and multi-pararametric three-dimensional treatment planning. Emerging evidence from prospective studies shows a high rate of local control throughout all stages, superior to two-dimensional brachytherapy, with limited toxicity for each organ site. This is associated with a high rate of pelvic control and overall survival. Based on clinical evidence, there is a dose-effect relationship for both disease and morbidity endpoints from which clear dose constraints for the target and organs at risk were derived. This review gives an overview of the major milestones that occurred in the development of image-guided adaptive brachytherapy in the last two decades, including outcome data and a summary of the hard and soft dose constraints recommended for targets and organs at risk.

Incidental axillary dose delivery to axillary lymph node levels I-III by different techniques of whole-breast irradiation: a systematic literature review.

BACKGROUND AND OBJECTIVE: In breast cancer treatment, radiotherapy is an essential component for locoregional management. Axillary recurrence in patients with invasive breast carcinoma remains an issue. The question of whether breast irradiation may unintentionally include levels I, II, and III, and may decrease the risk of axillary recurrence, remains a topic of discussion. PATIENTS AND METHODS: A literature search was performed in PubMed and the Cochrane Library to identify articles that have published data regarding dose-volume analysis of axillary levels in breast irradiation. The following MESH terms were used: "breast cancer/lymph nodes" AND "radiotherapy dosage." RESULTS: Thirteen articles were identified. The irradiation technique, initial dose prescribed to the breast, delineated volumes, and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using standard fields (ST) ranged between 22 and 43.5 Gy, 3 and 35.6 Gy, and 1.0 and 20.5 Gy, respectively. The average doses delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using "high tangential" fields (HT) ranged between 38 and 49.7 Gy, 11 and 47.1 Gy, and 5 and 44.7 Gy, respectively. Finally, the average doses delivered to axilla levels I, II, and III using intensity-modulated radiation therapy (IMRT) were between 14.5 and 42.6 Gy, 3.4 and 35 Gy, and 1.2 and 25.5 Gy, respectively. CONCLUSION: Our literature review suggests that the incidental dose delivered to the axilla during whole-breast irradiation is heterogenous and dependent on the irradiation technique used. However, whether this observation can be translated into a therapeutic effect is still a matter of debate.

Radiotherapy dose escalation on pelvic lymph node control in patients with cervical cancer.

OBJECTIVE: Data supporting dose escalation for node-positive cervical cancer are currently limited to small retrospective studies. The goal of this study was to assess whether radiation dose was associated with lymph node control or gastrointestinal toxicity in patients with node-positive cervical cancer. METHODS: A total of 390 patients with carcinoma of the uterine cervix were treated between October 1997 and October 2017. Patients included in our analysis were those with squamous cell carcinoma or adenocarcinoma who were node-positive, treated definitively, and with at least one follow-up visit and post-treatment imaging scan. We excluded those without follow-up and those treated with palliative intent. All patients were treated with external beam radiation to pelvic±para-aortic fields with concurrent weekly cisplatin. All lymph nodes present at the time of treatment were stratified by size as <2 cm or ≥2 cm. Acute and late gastrointestinal toxicity were recorded for all patients. RESULTS: A total of 77 patients with 206 lymph nodes were identified. Median stage at presentation was FIGO IIB. Thirteen patients underwent definitive surgical resection followed by adjuvant radiation, of which 12 were treated to doses ≤5040 (range 2700-5940) cGy. Sixty-four patients were treated with definitive chemoradiation, of which 42 (66%) received ≤5040 (range 4500-5040) cGy and 22 (34%) received >5040 (range 5300-6640) cGy. Patients with pre-chemoradiation lymph nodes ≥2 cm had inferior lymph node control compared with patients with pre-chemoradiation lymph node <2 cm at 12 months (77% vs 100%, p=0.002). Radiation dose >5040 cGy was not significantly associated with improved lymph node control compared with ≤5040 cGy when analyzing all patients (12 months, 100% vs 89%, p=0.112). In patients with pre-chemoradiation lymph nodes ≥2 cm, radiation dose >5040 cGy was associated with improved lymph node control (12 months, 100% vs 60%, p=0.020). Acute grade ≥2 gastrointestinal toxicity was not associated with radiation dose >5040 cGy (20% vs 13%, p=0.424). Two patients developed grade ≥2 late gastrointestinal toxicity, both of whom were treated to ≤5040 cGy. CONCLUSIONS: This series supports the role of dose escalation for patients with lymph nodes ≥2 cm. Dose escalation is associated with improved control in patients with larger lymph nodes, and is not associated with greater gastrointestinal toxicity.

Changes in the cervical microbiota of cervical cancer patients after primary radio-chemotherapy.

OBJECTIVE: Several recent studies have identified a potential interaction between the vaginal microbiota and gynecological cancers, but little is known about the cervical microbiota and its changes during cancer treatment. Therefore, the aim of the study was to evaluate the quantitative and qualitative changes of cervical microbiota in patients undergoing concurrent chemotherapy and radiation treatment for locally advanced cervical cancer. METHODS: Cervical cytobrush samples of 15 cervical patients undergoing chemoradiation treatment were collected 1 day before starting external beam radiation therapy and on the day of the last fraction of brachytherapy. After DNA extraction, 16S rRNA amplicon sequencing of the V3-V4 region was performed on the MiSeq platform, followed by data processing and statistical analyses concerning the alpha and beta diversity of 16 samples (7 samples were excluded because of incomplete sample sets). RESULTS: The amount of amplicon yield after polymerase chain reaction analysis in post-radiation samples was significantly lower compared with the baseline samples (pre 31.49±24.07 ng/µl; post 1.33±1.94 ng/µl; p=0.007). A comparison of pre-treatment and post-treatment samples did not show significant differences regarding beta diversity (weighted UniFrac). There was no significant difference in alpha diversity, which is used to characterize species diversity within a particular community and takes into account both number and abundance (Shannon Diversity Index pre-treatment samples: 2.167±0.7504 (95% CI 1.54 to 2.79); post-treatment samples: 1.97±0.43 (95% CI 1.61 to 2.33); p=0.38). Interindividual differences in patients could partly explain some variation of the samples (permutational multivariate analysis of variance). CONCLUSION: There was a strong reduction in cervical bacterial loads after chemoradiation. Neither alpha nor beta diversity varied significantly when baseline samples were compared with post-treatment samples.

Low-dose adjuvant vaginal cylinder brachytherapy for early-stage non-endometrioid endometrial cancer: recurrence risk and survival outcomes.

OBJECTIVE: The aim of this study was to evaluate recurrence patterns and survival outcomes for patients with early-stage non-endometrioid endometrial adenocarcinoma treated with adjuvant high-dose rate vaginal brachytherapy with a low-dose scheme. METHODS: A retrospective review was performed of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II non-endometrioid endometrial cancer who received adjuvant vaginal brachytherapy with a low-dose regimen of 24 Gy in six fractions from November 2005 to May 2017. All patients had >6 months of follow-up. Rates of recurrence-free survival, overall survival, vaginal, pelvic, and distant recurrence were calculated by the Kaplan-Meier method. Prognostic factors for recurrence and survival were evaluated by Cox proportional hazards modeling. RESULTS: A total of 106 patients were analyzed. Median follow-up was 49 months (range 9-119). Histologic subtypes were serous (47%, n=50), clear cell (10%, n=11), mixed (27%, n=29), and carcinosarcoma (15%, n=16). Most patients (79%) had stage IA disease, 94% had surgical nodal assessment, and 13% had lymphovascular invasion. Adjuvant chemotherapy was delivered to 75%. The 5-year recurrence-free and overall survival rates were 74% and 83%, respectively. By histology, 5-year recurrence-free/overall survival rates were: serous 73%/78%, clear cell 68%/88%, mixed 88%/100%, and carcinosarcoma 56%/60% (p=0.046 and p<0.01). On multivariate analysis, lymphovascular invasion was significantly associated with recurrence (HR 3.3, p<0.01). The 5-year vaginal, pelvic, and distant recurrence rates were 7%, 8%, and 21%, respectively. Vaginal and pelvic recurrence rates were highest for patients with carcinosarcoma, lymphovascular invasion and/or FIGO stage IB/II disease. At 5 years, vaginal and pelvic recurrence rates for patients with lymphovascular invasion were 33% and 40%, respectively. Patients with stage IA disease or no lymphovascular invasion had 5-year vaginal recurrence rates of 4% and pelvic recurrence rates of 6% and 3%, respectively. CONCLUSIONS: Adjuvant high-dose rate brachytherapy with a low-dose scheme is effective for most patients with early-stage non-endometrioid endometrial cancer, particularly stage IA disease and no lymphovascular invasion. Pelvic radiation therapy should be considered for those with carcinosarcoma, lymphovascular invasion and/or stage IB/II disease.

Clinical safety and efficacy of salvage reirradiation for upper abdominal malignancies.

PURPOSE: Reirradiation has the potential to provide effective local control of upper abdominal malignancies. This study aimed to evaluate the safety and efficacy of reirradiation for upper abdominal malignancies. METHODS: A total of 42 patients with a history of prior radiotherapy (RT) received reirradiation for abdominal malignancies between 2005 and 2017. Each patient's medical records, contours, and dose distribution for both RT courses were reviewed. The median dose of the prior RT was 50.0 Gy (range, 30.0-60.0 Gy) and the median dose of reirradiation was 45.0 Gy (range, 15.0-75.0 Gy). RESULTS: With a median follow-up of 10.9 months, the median infield-failure-free survival (IFFS) rate was 9.2 months. Gross tumor volume (GTV) significantly related to IFFS in both the univariate (p = 0.009) and multivariate analyses (p = 0.024), and patients with a GTV of <60.0 mL had an improved IFFS (p = 0.001). Four patients experienced ≥grade 3 late toxicities. In the retrospective dose reconstruction analysis in these patients, the cumulative dose to the most exposed 2 cc (D2cc) of the duodenum was >60.0 Gy (range, 60.1-73.7 Gy). In the univariate analysis, the D2cc of the duodenum and a preexisting duodenal ulcer identified using endoscopy prior to reirradiation significantly correlated with late severe toxicity (p = 0.021 and 0.017, respectively). CONCLUSIONS: Reirradiation for upper abdominal malignancies could be safely performed for patients without preexisting gastrointestinal morbidity unless the duodenum received excessive radiation doses. Reirradiation could also provide substantial IFFS, especially for patients with a GTV of <60.0 mL.

[3D printing non-coplanar template-assisted 125-iodine seed implantation for thorax movement tumor: individual template design method].

Objective: To compare the dosimetric data between preoperative plans and postoperative verification in computed tomography CT-guided and 3D printing template-assisted 125-iodine ((125)I) seed implantation for thorax movement tumor and to explore the feasibility and accuracy of the individualized template design method. Methods: A total of 35 patients, 20 males and 15 females with median age of 62 (17-87) years old, who registered from January 2016 to December 2017 applied with 3D printing guided template assisted radioactive seed implantations in Peking University Third Hospital were included in this study. (125)I seeds with a prescribed dose of 110-180 Gy were impanted. 3D printing templates were designed and produced for 35 cases. The dosimetric parameters: D(90), minimum peripheral dose (mPD), V(100), V(150), V(200), conformal index (CI), external index (EI), and homogeneity index (HI) were compared between pre-and post-plannings. Statistical method was two group of related non-parameters test. Results: The design and production of 35 cases' templates were in place well. Compared with the preoperative planning, the postoperative D(90), V(100), V(150), V(200), mPD, CI, EI and HI differences were 5.57%, 0.34%, 0.33%, -1.20%, 21%, 2.8%, -14.2%, 4.71%, -10.4%. All the included dosimetry parameters changed slightly after surgery compared with before surgery, but the difference was not statistically significant(all P>0.05). Conclusions: The dosimetric parameters of postoperative verification are consistent well with the preoperative planning and have good accuracy, the results could meet the clinical requirements.

[Dosimetric comparison of the helical tomotherapy, intensity-modulated radiotherapy and volumetric-modulated arc therapy in radical radiotherapy for esophageal cancer].

Objective: To compare the dosimetric parameters of three different modern radiation techniques in radical radiotherapy for esophageal cancer. Methods: A total of 25 patients with pathologically confirmed esophageal squamous cell carcinoma in Zhejiang Cancer Hospital were included from September 2015 to May 2016 and three radiation treatment plans for helical tomotherapy (TOMO), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) were designed respectively for each patient. Study patients included 24 males and 1 female,aged from 47 to 82 years old, with a median age of 63 years old. All patients received the total prescription dose of 60 Gy in 30 fractions to the planning target volume (PTV). Conformity index (CI), heterogeneity index (HI), D(1), D(2), D(50), D(95), D(98), D(9)9 and V(95), V(100), V(105) of PTV was calculated. The mean dose, V(5), V(10), V(20), V(30), V(40) and V(50) of total lung, heart, and maximum dose (D(max)) to spinal cord were recorded as well. Results: Compared with TOMO and IMRT, VMAT showed higher CI (0.81±0.08) and lower HI (0.10±0.05), and CI was worse in IMRT (0.77±0.05) than TOMO (0.79±0.04) (t=2.604, P=0.016) and VMAT (t=2.817, P=0.010). There was no significant difference in HI among three radiation techniques. The dosimetric parameters of TOMO in normal lung were significantly better than those of VMAT and IMRT, especially in V(20) and V(30). The D(max) of spinal cord (38.24±3.72) Gy in TOMO was significantly lower than that of the VMAT ((39.88±3.27)Gy, t=-3.173, P=0.004) and IMRT plan ((41.09±3.18)Gy, t=-5.559, P=0.000). Subgroup analysis showed that VMAT was superior to TOMO and IMRT in CI and HI, especially HI (0.09±0.01) significantly better than TOMO (0.12±0.03, t=3.024, P=0.029) and IMRT (0.12±0.02, t=-3.800, P=0.013) for patients with cervical and upper thoracic esophageal cancer. TOMO and VMAT were significantly better than IMRT in MLD, lung V(20) and V(30) (all P<0.05). TOMO (38.46±2.15)Gy was significantly superior to VMAT ((41.02±1.28)Gy,t=-2.701, P=0.043) and IMRT ((41.76±1.11)Gy, t=-3.111, P=0.027) at D(max) of the spinal cord. For the patients with middle and lower thoracic esophageal cancer, TOMO, VMAT and IMRT had no statistically significant differences in CI and HI. IMRT was inferior to TOMO and VMAT in MLD, lung V(10), V(20), and V(30) (all P<0.05). TOMO (38.17±4.14) Gy was significantly superior to VMAT ((39.52±3.64)Gy,t=-2.219, P=0.040) and IMRT ((40.87±3.59)Gy,t=-4.528, P=0.000) at D(max) of the spinal cord. Conclusions: The VMAT plan is better than TOMO and IMRT in terms of the conformal degree and dose uniformity of the target volume.TOMO seems significantly better than VMAT and IMRT in protecting normal tissue.

[Comparison of preoperative planning of radioactive seed implantation for pelvic wall recurrent gynecological malignant tumors between 3D-printing non-coplanar template and 3D-printing coplanar template].

Objective: To compare the difference of preoperative planning parameters between 3D-printing non-coplanar template (3D-PNCT) and 3D-printing coplanar template (3D-PCT) in the treatment of pelvic wall recurrent gynecological malignant tumor with radioactive seeds implantation, and to guide the clinical application. Methods: From January 2016 to March 2018, 33 patients with pelvic wall recurrent gynecological malignant tumor were treated with radioactive seeds implantation assisted by 3D-printing template and in Peking University Third Hospital. All patients underwent 3D-PNCT and 3D-PCT preoperative planning. The D(90) of target remained similar for the same patient. The parameters were compared with Wilcoxon test or Kruskal-Wallis test. Results: D(90) was similar between the two groups (P>0.05). The number of inserting needles through intestine and bone in 3D-PNCT group was less than that in 3D-PCT group (0 (0-13), 0 (0-25), Z=-2.941, P<0.05;0 (0-3), 0 (0-25), Z=-2.232, P<0.05). Conclusion: For patients with gynecological malignancies with pelvic recurrence, both of the two peroperative plans could achieve prescription dose, but 3D-PNCT is more safer.

[Cognitive deficits following brain tumor radiation therapy]. / Kognitive Defizite nach Strahlentherapie von Hirntumoren.

Brain radiation is an important treatment option for malignant and benign brain diseases. The possible acute or chronic impact of radiation therapy on cognitive performance is important for daily functioning and quality of life. A detailed evaluation of cognitive impairment is important in the context of how to control disease progression. The susceptibility of the hippocampus to radiation-induced neuronal damage and its important role in memory highlight that therapeutic strategies require precision medicine.

[The effect of pre-operation (125)I seed activity measuring on dose accuracy].

Objective: To measure the activity of (125)I seed and compare the dose difference of ten patients treated with seed implantation in pre-plan with actual seed activity and calibrate activity. Method: The activity of 100 seeds from company A and B was measured with a well-type ionization chamber 1 day before operation and named group A and B. The activity of two groups was compared and the error between actual and calibrate activity (22.2 MBq, group C) was calculated. Ten patients implanted with (125)I seeds from November 1 st to 30 th, 2017, solstice 30 were selected in Hebei General Hospital. Firstly, pre-plans were designed with 22.2 MBq, prescribed dose were 100-140 Gy. The dose parameters of 90% volume absorbed dose (D(90)), 150% volume fraction (V(150)) and 100% volume fraction (V(100)) were calculated. Then changed 22.2 MBq to actual activity of group A and B, calculated the dose parameters above again. Then dose parameters of D(90), V(150), V(100) in group C were compared with those in group A and B respectively. Result: The actual activity 1 day before the operation was(22.6±0.7)and(23.9±0.9)MBq in group A and B respectively. Compared with 22.2 MBq, the difference was statistically significant(t=5.7, P<0.05 and t=19.2, P<0.05), and the activity error of group B was greater than 5%. The D(90) of group A, B and C were (124.3±9.7) , (131.2±10.2) and (121.9±9.5) Gy respectively.The V(150) were 58.4%±9.4%, 63.7%±8.9% and 56.5%±9.2% respectively. The V(100) were 88.9%±5.0%, 92.0%±4.1%, 88.1%±5.2% respectively.The difference of D(90) between calibrate activity(group C) and actual activity(group A and B) were statistically significant (t=40.2, P<0.05 and t=40.3, P<0.05). The difference of V(150) between group C and group A and B were statistically significant (t=7.5, P<0.05 and t=24.7, P<0.05). The difference of V(100) between group C and group A and B were statistically significant (t=6.6, P<0.05 and t=7.3, P<0.05). Conclusion: There is difference between the actual activity and calibration activity. The difference affects the dose parameters in pre-plan.The seed activity should be measured before operation strictly and the pre-plan should be designed with the actual activity.

[Efficacy and dosimetric analysis of (125)I seeds implantation for pelvic recurrent cervical cancer after radiotherapy under CT guidance].

Objective: To evaluate the relationship of dosimetry parameters and efficacy of (125)I seeds implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy(EBRT) under CT guidance. Methods: A retrospective analysis was made on 30 PRCC patients after EBRT in Peking University Third Hospital with (125)I seeds implantation under CT guidance. Postoperative plans were made to evaluate the dosimetric parameters. Kaplan-Meier method was used to calculate local progression free survival (LPFS) rate and overall survival (OS) rate, and Log-rank test and Cox regression were used for univariate and multivariate analysis. Results: The 1-year and 2-year LPFS rate was 39.4% and 22.5%, respectively. The 1-year and 2-year OS rate was 57.3% and 27.4%, respectively. On postoperative plan, D(90) was (132±47) Gy, D(100) was (51±24) Gy, V(100) was 88%±10%, V(150)was 69%±15%, V(200) was 51%±18%.LPFS time would be longer while D(90) ≥105 Gy or D(100) ≥ 55 Gy or V(100) ≥ 91% (all P<0.05). D(100) was significantly related to LPFS (P<0.05). But these dosimetry parameters got no effect on OS. Conclusions: LPFS time of (125)I seeds implantation for PRCC after EBRT under CT guidance would be longer when D(90)≥105 Gy or D(100)≥ 55 Gy, or V(100)≥ 91%. D(100) is an independent factor related to LPFS.

[Brachytherapy treatment planning calculation (125)I particle esophageal stent dosimetric study].

Objective: To investigate the dosimetric distribution characteristics of (125)I seed stents with different seed spacing, diameter and length, as well as different (125)I seed activity. The dosimetry table of (125)I seed esophageal stent was derived to provide dosimetry for its clinical application. Methods: The self-expanding coated esophagus stent was designed to carry radioactive (125)I seeds with different length, diameter and seed spacing. A cylindrical organic glass model (Thickness 0.8 cm, diameter 20 cm, height 20 cm) was fixed vertically to a cylindrical organic glass containing a solid paraffin (analytical pure) solution. After paraffin cooling and solidification, CT scan was used to transmit image information to TPS. With the center of the bracket as a dot, the cumulative dose at a distance of 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0 and 8.0 cm away from the dot was simulated respectively in 0° and 9° direction. Results: The radial cumulative dose with the seed spacing which was 1.0 and 1.5 cm were different by 4.8%, 5.8%, 7.2%, 8.0%, 8.6% and 13.3% respectively under the exposure of 18.5, 22.2, 25.9, 29.6, 33.3 and 37.0 MBq. When the seed spacing was the same as the length of the stent, the radial cumulative dose with the stent which diameter was 1.3, 2.0, 2.4 cm were different by 4.9% vs 3.4%, 4.7% vs 3.8%, 5.4% vs 6.6%, 4.5% vs 5.3%, 4.7% vs 4.8%, 4.8% vs 5.4% respectively under the exposure of 18.5, 22.2, 25.9, 29.6, 33.3 and 37.0 MBq. When the seed spacing was the same as the diameter of the stent, the radial cumulative dose with the stent which length was 8, 12, 16 cm were different by 1.9% vs 1.2%, 1.7% vs 0.8%, 1.6% vs 1.3%, 1.9% vs 1.5%, 1.7% vs 1.8%, 1.6% vs 1.3% respectively under the exposure of 18.5, 22.2, 25.9, 29.6, 33.3 and 37.0 MBq. Conclusions: The radial cumulative dose of the (125)I seed stent is positively correlated with the activity of the radioactive seeds, Which means the dose rate of a certain point of the (125)I seed stent increase with the increase of the activity of the radioactive seeds. The stent of the (125)I radioactive seeds is negatively correlated with the distance, the dose rate of the (125)I seed stents decrease rapidly with the increase of distance.

[Occurrence of radiation-induced injury in vagina after radical radiotherapy of cervical cancer and its affecting factors].

Objective: To investigate the occurrence and degree of radiation-induced injury in vagina after radical radiotherapy of cervical cancer. Methods: A total of 282 cases of patients with cervical cancer were collected from November 2016 to September 2017. All of the above patients underwent radical radiotherapy from 2008 to 2017 in the First Affiliated Hospital of Xi'an Jiaotong University. The patients' International Federation of Gynecology and Obstetrics (FIGO) staging (2009) , brachytherapy dose, whether receive synchronous chemotherapy or not, age and body mass index (BMI) for the occurrence and severity of vaginal radiation injury at different time periods were analyzed by cross-sectional survey method. The single factor would be analyzed by the method of Chi-square test and the multiple factors would be analyzed by logistic regression method to checkout. Results: Of the 282 patients, the incidence of radiation-injury in vaginal was 84.4% (238/282) , with the incidence rate of degree Ⅰ,Ⅱ and Ⅲ radiation injury were respectively 50.7% (143/282), 29.8% (84/282) and 3.9% (11/282; χ(2)=153.375, P<0.05) , and there was no degree Ⅳ. Until the end of the follow-up time, the incidence of radiation-induced injury in vaginal after completing the treatment within 1 year, 1-2 years,>2-<5 years and ≥5 years were respectively 80.0% (24/30) , 87.2% (102/117) , 88.2% (60/68) and 77.6% (52/67; χ(2)=4.231, P=0.238) . There were 30 cases be followed within 1 year after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ of radiation injury in vagina was 60.0% (18/30) , 20.0% (6/30) and 0, respectively (χ(2)=28.636, P<0.05). There were 117 cases be followed between 1-2 years after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ vaginal radiation-induced injury were 54.7% (64/117) , 29.9% (35/117) and 2.6% (3/117) , respectively (χ(2)=77.198, P<0.05) . There were 68 cases be followed between >2-<5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation-induced injury were 51.5% (35/68) ,33.8% (23/68) and 2.9% (2/68) , respectively (χ(2)=39.525, P<0.05) . There were 67 cases be followed ≥5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation injury were 38.8% (26/67) , 29.9% (20/67) and 9.0% (6/67) , respectively (χ(2)=16.395, P<0.05) . The single-factor analysis result indicated that the brachytherapy dose had an obvious effect on vaginal radiation-induced injury (χ(2)=5.344, P=0.021) ; however, other factors, such as age, BMI, FIGO stages and synchronous chemotherapy, had no obvious effect on vaginal radiation-induced injury (all P>0.05) . The multifactor analysis indicated that the brachytherapy dose was an independent factor affecting the occurrence of vaginal radiation-induced injury (P=0.043) . Conclusion: After the radical radiotherapy of cervical cancer, the vaginal radiation-induced injury is associated with the dose of brachytherapy.

Radiotherapy of Glioblastoma 15 Years after the Landmark Stupp's Trial: More Controversies than Standards?

BACKGROUND: The current standard of care of glioblastoma, the most common primary brain tumor in adults, has remained unchanged for over a decade. Nevertheless, some improvements in patient outcomes have occurred as a consequence of modern surgery, improved radiotherapy and up-to-date management of toxicity. Patients from control arms (receiving standard concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide) of recent clinical trials achieve better outcomes compared to the median survival of 14.6 months reported in Stupp's landmark clinical trial in 2005. The approach to radiotherapy that emerged from Stupp's trial, which continues to be a basis for the current standard of care, is no longer applicable and there is a need to develop updated guidelines for radiotherapy within the daily clinical practice that address or at least acknowledge existing controversies in the planning of radiotherapy.The goal of this review is to provoke critical thinking about potentially controversial aspects in the radiotherapy of glioblastoma, including among others the issue of target definitions, simultaneously integrated boost technique, and hippocampal sparing. CONCLUSIONS: In conjunction with new treatment approaches such as tumor-treating fields (TTF) and immunotherapy, the role of adjuvant radiotherapy will be further defined. The personalized approach in daily radiotherapy practice is enabled with modern radiotherapy systems.

Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area.

BACKGROUND & AIMS: This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT). METHODS: We retrospectively reviewed the records of 985 patients who received radiotherapy (RT) for PVTT. The median equivalent RT dose was 48.75 Gy. Combined treatment, defined as liver-directed treatments performed within a month of RT, was administered to 657 patients (66.7%). The PVTT and primary tumour were irradiated in 413 patients (41.9%), and PVTT only was targeted in 572 patients (58.1%). RESULTS: The response rate of the PVTT was 51.8%, and RT responders had a significantly longer survival than non-responders (15.2 vs. 6.9 months). Equivalent RT dose and combined treatment predicted response of PVTT. The median overall survival (OS) was 10.2 months. Multivariate analysis revealed the equivalent RT dose ˃45 Gy and combined treatment as significant positive factors for OS. In the propensity score matching analysis, the combined treatment group had better OS than the no combined treatment group, whereas the OS of the PVTT + primary tumour group did not differ significantly from that of the PVTT only group. CONCLUSION: The equivalent RT dose ˃45 Gy, given in combination with other treatments, provided better PVTT control and OS. The optimal RT volume is suggested for either PVTT + primary or PVTT only. Taken together, multimodal treatment with equivalent RT dose higher than 45 Gy is recommended for patients with HCC and PVTT.

[Dosimetry verification of radioactive seed implantation with 3D printing template and CT guidance for paravertebral/retroperitoneal malignant tumor].

Objective: To compare the dose distributions of postoperative plans with preoperative plans for seeds implantations of paravertebral/retroperitoneal tumors assisted by 3D printing guide template and CT guidance, explore the effects of the technology for seeds implantations in dosimetry level and provide data support for the optimization and standardization in seeds implantation. Methods: Between December 2015 and July 2016, a total of 10 patients with paravertebral/retroperitoneal tumors (12 lesions) received 3D printing template assist radioactive seeds implantations in department of radiation oncology of Peking University Third Hospital, and included in the study. The diseases included cervical cancer, kidney cancer, abdominal stromal tumor, leiomyosarcoma of kidney, esophageal cancer and carcinoma of ureter. The prescribed doses was 110-150 Gy. All patients received preoperative planning design, individual template design and production, and the dose distribution of postoperative plan was compared with preoperative plan. Dose parameters including D(90), MPD, V(100), V(150,)conformal index(CI), EI of target volume and D(2cc) of organs at risk (spinal cord, aorta, kidney). Statistical software was SPSS 19.0 and statistical method was non-parameters Wilcoxon symbols test. Results: A total of 10 3D printing templates were designed and produced which were including 12 treatment areas.The mean D(90) of postoperative target area (GTV) was 131.1 (97.8-167.4 Gy) Gy. The actual seeds number of post operation increased by 3 to 12 in 5 cases (42.0%). The needle was well distributed. For postoperative plans, the mean D(90,)MPD, V(100,)V(150) was 131.1 Gy, 69.3 Gy, 90.2% and 65.2%, respectively, and which was 140.2 Gy, 65.6 Gy, 91.7% and 26.8%, respectively, in preoperative plans. This meant that the actual dose of target volume was slightly lower than preplanned dose, and the high dose area of target volume was larger than preplanned range, but there was no statistical difference in P value between the two groups except V(150)(P=0.004). The actual dose conformity of target volume was worse than preplanned (CI was 0.58 and 0.62, respectively) and the difference was statistically significant(P=0.019). The actual dose of external target volume was higher than preplanned (EI was 55% and 45.9%, respectively) and the difference had no significance. For organs at risk, the actual mean D(2cc) of spinal cord, aorta and kidney was 24.7, 54.4 and 29.7 Gy, respectively, which was higher than preplanned(20.6, 51.6 and 28.6 Gy, respectively), and there was no significant difference in two groups. Conclusions: Most parameters of postoperative validations for 3D printing template assisted seeds implantation in paravertebral/retroperitoneal are closed to the expectations of preoperative plans which means the improvement of accuracy in treatment.

[Evaluation of CT-guided iodine-125 seeds brachytherapy for intracranial malignant tumors under control of target and dose].

Objective: To assess the efficacy and safety of CT-guided iodine-125 seeds in the treatment of intracranial malignancies under control of target and dose. Methods: From November 2003 to May 2016, with the clinical data of 412 operations on 310 patients in 12 hospitals in the past 14 years, this study analyzed the method of CT guided iodine-125 particles brachytherapy in the treatment of intracranial malignant tumors and evaluated the efficacy and complications. Stratification analysis of intracranial malignant tumors was performed. Results: Overall survival (OS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 67, 41, 26, 23, 46 months respectively.And the progression free time (PFS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 42, 6, 9, 11, 12 months respectively.Various complications were observed with a relatively low incidence of 10.4%.Three cases deceased at an interval of 7-45 days after treatment. Conclusions: For patients with intracranial malignancies, iodine-125 seeds brachytherapy could achieve a satisfactory treatment efficacy with tolerated complications.Iodine-125 seeds brachytherapy may act as a first-line regimen.