Search

Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased α-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings.

Purpose: To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy., Materials and Methods: Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm 2 , were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor. Pixelwise ADC maps were correlated with histological metrics including nuclear counts, nuclear sizes, nuclear spaces, cytoplasmic spaces, and extracellular spaces., Results: As compared with the nonirradiated region, the irradiated region exhibited significant increases in ADC, extracellular space, and nuclear size, and a significant decrease in nuclear counts (P < 0.001 for all). Optimal ADC to differentiate the irradiated from nonirradiated regions was achieved at a b-value of 800 s/mm 2 by the two-point method and monoexponential curve fitting. ADC positively correlated with extracellular spaces (r = 0.74) and nuclear sizes (r = 0.72), and negatively correlated with nuclear counts (r = -0.82, P < 0.001 for all)., Conclusion: As a radiomic biomarker, ADC maps correlating with histological metrics pixelwise could be a means of evaluating tumor heterogeneity and responses to radiotherapy., Level of Evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:483-489., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. Methods: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39–60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. Results: The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. Conclusions: This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. Trial registration: ClinicalTrials.gov NCT04951921, registered 7 July 2021. Relevance statement: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. Key points: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy. [ABSTRACT FROM AUTHOR]

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients.Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS).Results: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS.Conclusion: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB-IV cervical cancer following concurrent chemoradiotherapy (CCRT).Methods: We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB-IV cervical cancer treated with CCRT in 2007-2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24-92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models.Results: The median follow-up time for surviving patients was 69 months (range, 9-126 months). Non-squamous cell type, ADC10 <0.77 × 10-3 mm2/s, T3-4, M1 stage and high-risk HPV status were selected to generate a model, in which the OS and DFS for the low, intermediate and high-risk groups were significantly stratified (p < 0.0001). The prognostic model improved the prediction significantly compared with the International Federation of Gynaecology and Obstetrics (FIGO) stage for both the training and independent testing datasets (p < 0.0001).Conclusions: The prognostic model based on integrated clinical and imaging data could be a useful clinical biomarker to predict OS and DFS in patients with stage IB-IV cervical cancer treated with CCRT.Key Points: • ADC 10 is the best prognostic factor among ADC parameters in cervical cancer treated with CCRT • A novel prognostic model was built based on histology, ADC 10 , T and M stage and HPV status • The prognostic model outperforms FIGO stage in the survival prediction. [ABSTRACT FROM AUTHOR]

Purpose: To compare the long-term outcomes in patients with salivary gland adenoid cystic carcinoma (SGACC) treated with post-operative chemoradiotherapy (POCRT) versus post-operative radiotherapy (PORT).Methods: We retrospectively reviewed the records of 91 SGACC patients treated with surgery followed by PORT (n = 58) or POCRT (n = 33) between 2000 and 2013. Treatment outcomes between groups were compared using propensity score matching (1:1 nearest neighbor).Results: The median radiation dose was 66 Gy, and patients were followed up for a median of 71 months. Cisplatin-based concurrent regimens were the most commonly used chemotherapy schedules. In the entire study cohort, patients undergoing POCRT showed a trend toward higher locoregional control (LRC) rates than those treated with PORT alone at both 5 and 8 years (97 and 97 % versus 84 and 79 %, respectively; P = .066). Distant metastases were the most common form of treatment failure and occurred in 31 (34 %) patients (PORT, n = 17; POCRT, n = 14). After propensity score matching (33 pairs), patients receiving POCRT had 5- and 8 year LRC rates of 97 and 97 %, respectively, compared with 79 and 67 % for patients treated with PORT alone (P = .017). The two groups did not differ significantly in terms of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). However, a significantly better opioid-requiring pain-free survival (ORPFS) was achieved in POCRT group (P = .038). Subgroup analyses revealed that patients with stage III - IV disease (P = .040 and .017), positive surgical margins (P = .011 and .050), or perineural invasion (P = .013 and .035) had significantly higher 5- and 8 year LRC and ORPFS when treated with POCRT, respectively.Conclusions: In SGACC patients, adding concurrent chemotherapy to PORT may increase LRC and ORPFS rates, particularly in presence of stage III - IV disease, positive surgical margins, or perineural invasion. However, no significant differences in DMFS, DFS, and OS were observed. [ABSTRACT FROM AUTHOR]

Purpose: To study the outcomes of patients with adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix primarily treated with radiotherapy (RT), identify the prognostic factors, and evaluate the efficacy of concurrent chemoradiotherapy (CCRT) or salvage surgery. Methods and Materials: A total of 148 patients with Stage I-IVA AC/ASC of cervix after full-course definitive RT were included. Of the 148 patients, 77% had advanced stage disease. Treatment failure was categorized as either distant or local failure. Local failure was further separated into persistent tumor or local relapse after complete remission. The effectiveness of CCRT with cisplatin and/or paclitaxel was examined, and the surgical salvage rate for local failure was reviewed. Results: The 5-year relapse-free survival rate was 68%, 38%, 49%, 30%, and 0% for those with Stage IB/IIA nonbulky, IB/IIA bulky, IIB, III, and IVA disease, respectively, and appeared inferior to that of those with squamous cell carcinoma of the cervix treated using the same RT protocol. Incomplete tumor regression after RT, a low hemoglobin level, and positive lymph node metastasis were independent poor prognostic factors for relapse-free survival. CCRT with weekly cisplatinum did not improve the outcome for our AC/ASC patients. Salvage surgery rescued 30% of patients with persistent disease. Conclusion: Patients with AC/ASC of the cervix primarily treated with RT had inferior outcomes compared to those with squamous cell carcinoma. Incomplete tumor regression after RT was the most important prognostic factor for local failure. Salvage surgery for patients with persistent tumor should be encouraged for selected patients. Our results did not demonstrate a benefit of CCRT with cisplatin for this disease. [ABSTRACT FROM AUTHOR]

Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy. Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method. Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group. Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration. [ABSTRACT FROM AUTHOR]

• LMR significantly changed during RT in patients with head and neck cancer. • The dynamic changes in LMR during RT carried prognostic value. • Longitudinal assessment of LMR during RT may serve as a promising biomarker. We sought to investigate whether dynamic changes in lymphocyte-to-monocyte ratio (LMR) occurring during the course of radiotherapy (RT) may have prognostic value in patients with head and neck cancer (HNC). We retrospectively reviewed the clinical records of patients with HNC who underwent RT at our center between 2005 and 2013. Generalized estimating equations were used to longitudinally assess changes in LMR through the course of RT. Delta-LMR was calculated as the difference between LMR measured during treatment and baseline LMR values. Freedom from metastasis (FFM) and overall survival (OS) served as the main outcome measures. A total of 1431 patients with HNC were enrolled. After a median follow-up of 9 years, 636 (44.4%) patients died and 240 (16.8%) had distant metastases. Compared with patients with low delta-LMR at two weeks, those with high delta-LMR experienced less favorable outcomes (five-year OS: 73% versus 59%, respectively, p < 0.001; five-year FFM: 87% versus 80%, respectively, p = 0.015). Similar findings were observed for delta-LMR measured at four weeks (five-year OS: 72% versus 60%, p < 0.001; five-year FFM: 86% versus 79%, respectively, p = 0.002) and six weeks (five-year OS: 72% versus 57%, p < 0.001; five-year FFM: 87% versus 79%, respectively, p = 0.002). Multivariate analysis identified delta-LMR as an independent prognostic factor for both FFM and OS. Delta-LMR is a simple and inexpensive biomarker that may be clinically useful for predicting FFM and OS in patients with HNC treated with RT. [ABSTRACT FROM AUTHOR]

The management of residual nonfunctional pituitary tumors after surgical resection remains controversial. In this study, we compared the prognosis of postoperative radiation therapy and observation only in patients with residual nonfunctional pituitary adenoma and reviewed the long-term complications after radiation therapy. We retrospectively analyzed 90 patients who underwent surgery for nonfunctional pituitary adenomas from January 2008 to April 2012. Residual tumors were classified by size, location, and pathologic staining. Tumor progression was defined as volume progression ≥15% with or without clinical symptoms. Postoperative radiation therapy was performed <1 year after the last surgery. We compared the progression and 3-year and 5-year progression-free survival between the observation group and postoperative radiation therapy group. Postradiation complications including hypopituitarism, diabetes insipidus, deterioration in visual field or acuity, cranial nerve palsy, and hydrocephalus were also analyzed. More of the patients who received postoperative radiation therapy had a tumor progression-free survival of ≥3 years than did those who did not receive postoperative radiation therapy. Postoperative radiation therapy was significantly beneficial for the patients with a tumor size ≥3 cm or with tumors in the cavernous sinus. The most frequent complication after radiation therapy was hypopituitarism and a few cases had third cranial nerve palsy; however, there were no significant relationships with radiation therapy. In this study, immediate radiation therapy after tumor resection was an effective and relatively safe treatment for residual or progressive nonfunctional pituitary adenomas. Moreover, the long-term complications of radiation therapy were mild. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the density heterogeneity pattern as a factor affecting Bragg peak degradation, including shifts in Bragg peak depth ( Z BP ), distal range ( R 80 and R 20 ), and distal fall-off ( R 80 – R 20 ) using Monte Carlo N-Particles, eXtension (MCNPX). Density heterogeneities of different patterns with increasing complexity were placed downstream of commissioned proton beams at the Proton and Radiation Therapy Centre of Chang Gung Memorial Hospital, including one 150 MeV wobbling broad beam (10×10 cm 2 ) and one 150 MeV proton pencil beam (FWHM of cross-plane=2.449 cm, FWHM of in-plane=2.256 cm). MCNPX 2.7.0 was used to model the transport and interactions of protons and secondary particles in density heterogeneity patterns and water using its repeated structure geometry. Different heterogeneity patterns were inserted into a 21×21×20 cm 3 phantom. Mesh tally was used to track the dose distribution when the proton beam passed through the different density heterogeneity patterns. The results show that different heterogeneity patterns do cause different Bragg peak degradations owing to multiple Coulomb scattering (MCS) occurring in the density heterogeneities. A trend of increasing R 20 and R 80 – R 20 with increasing geometry complexity was observed. This means that Bragg peak degradation is mainly caused by the changes to the proton spectrum owing to MCS in the density heterogeneities. In contrast, R 80 did not change considerably with different heterogeneity patterns, which indicated that the energy spectrum has only minimum effects on R 80 . Bragg peak degradation can occur both for a broad proton beam and a pencil beam, but is less significant for the broad beam. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively investigate whether postoperative low-pelvic radiotherapy (RT) is an appropriate treatment for node-negative, high-risk Stage I–IIA cervical cancer patients.Methods and Materials: A total of 228 Stage I–IIA cervical cancer patients treated by radical surgery and postoperative RT were included in this study. All patients had histopathologically negative pelvic node metastasis, but at least one of the following risk factors: parametrial involvement, positive or close resection margins, invasion depth two-thirds or greater cervical stromal thickness. Seventy-nine patients (35%) received 30–50 Gy (median 44) to whole pelvis and a boost dose to the low pelvis (whole-pelvic RT group); the other 149 patients (65%) received low-pelvic RT only (low-pelvic RT group). For both groups, the total external RT dose to the low pelvis ranged from 40 to 60 Gy (median 50). The potential factors associated with survival, small bowel (gastrointestinal) complications, and leg lymphedema were analyzed, and patients who had a relapse in the upper pelvis were identified.Results: The 5-year overall and disease-specific survival rate was 84% and 86%, respectively. After multivariate analysis, only bulky tumor (≥4 cm) and non-squamous cell carcinoma were significantly associated with survival. Parametrial involvement, lymph-vascular invasion, ≤50.4 Gy to the low pelvis, positive or close margins, and low-pelvic RT alone did not significantly affect survival. Grade I–V small bowel complications occurred in 33 patients (15%). Whole pelvic RT and >50.4 Gy to the low pelvis, but not old age and treatment technique (AP-PA vs. box), were significantly associated with gastrointestinal complications. Three patients (2%) in the low-pelvic RT group and 6 patients (8%) in the whole-pelvic RT group were found to have Grade III or higher small bowel complications (p = 0.023). Thirty-one percent of patients developed lymphedema of the leg. A dose to the low pelvis >50.4 Gy and an AP-PA field, but not whole-pelvic RT, old age, or the number of sampled lymph nodes, were associated with lymphedema of the leg. Five patients (3.6%) of the low-pelvic RT group and none of the whole-pelvic RT group developed upper pelvis relapse. Three of these 5 patients had upper pelvic relapse alone.Conclusion: Compared with whole-pelvic RT plus low-pelvic boost, low-pelvic RT alone significantly reduces the small bowel complications in node-negative, high-risk, Stage I–IIA cervical cancer patients. Although low-pelvic RT alone increases the incidence of upper pelvic relapse, its effect on survival is not substantial. Low-pelvic RT alone appears to be an appropriate treatment method for this group of patients. [Copyright &y& Elsevier]