Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.     

Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models

Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.     

Preoperative chemoradiotherapy for locally advanced low rectal cancer using intensity-modulated radiotherapy to spare the intestines: a single-institutional pilot trial

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3–4, N0–2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V_{15 Gy}) < 120 cc and V_{45 Gy} ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V_{15 Gy} was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses.     

Viral transmission and evolution dynamics of SARS-CoV-2 in shipboard quarantine

ObjectiveTo examine transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in shipboard quarantine of the Diamond Princess cruise ship.MethodsWe obtained the full SARS-CoV-2 genome sequences of 28 samples from the Global Initiative on Sharing All Influenza Data database. The samples were collected between 10 and 25 February 2020 and came for individuals who had been tested for SARS-CoV-2 during the quarantine on the cruise ship. These samples were later sequenced in either Japan or the United States of America. We analysed evolution dynamics of SARS-CoV-2 using computational tools of phylogenetics, natural selection pressure and genetic linkage.FindingsThe SARS-CoV-2 outbreak in the cruise most likely originated from either a single person infected with a virus variant identical to the WIV04 isolates, or simultaneously with another primary case infected with a virus containing the 11083G > T mutation. We identified a total of 24 new viral mutations across 64.2% (18/28) of samples, and the virus evolved into at least five subgroups. Increased positive selection of SARS-CoV-2 were statistically significant during the quarantine (Tajima’s D: −2.03, P < 0.01; Fu and Li’s D: −2.66, P < 0.01; and Zeng’s E: −2.37, P < 0.01). Linkage disequilibrium analysis confirmed that ribonucleic acid (RNA) recombination with the11083G > T mutation also contributed to the increase of mutations among the viral progeny.ConclusionThe findings indicate that the 11083G > T mutation of SARS-CoV-2 spread during shipboard quarantine and arose through de novo RNA recombination under positive selection pressure.     

Burnout of the US midwifery workforce and the role of practice environment

ObjectivesTo determine the prevalence of burnout among the midwifery workforce and the association between fixed personal and practice characteristics and modifiable organizational factors, specifically practice environment, to burnout among midwives in the United States.Data SourcePrimary data collection was conducted via an online survey of the complete national roster of certified nurse‐midwives and certified midwives over 3 weeks in April 2017.Study DesignThe study was a cross‐sectional observational survey consisting of 95 items about personal and practice characteristics, respondents'' practice environments, and professional burnout.Data Collection MethodsThe inclusion criterion was actively practicing midwifery in the United States. Data were analyzed with bivariate analyses to determine the association between personal and practice characteristics and burnout. A hierarchal multilinear regression evaluated the interrelationship between personal and practice characteristics, practice environment, and burnout.Principal FindingsOf the almost one third (30.9%) of certified nurse‐midwives and certified midwives who responded to the survey, 40.6% met criteria for burnout. Weak negative correlations existed between burnout and indicators of career longevity: age (r(2256) = −0.09, p < 0.01), years as a midwife (r(2267) = −0.07, p = 0.01), and years with employer (r(2271) = −0.05, p = 0.02). There were significant relationships between burnout score and patient workload indicators: patients per day in outpatient setting (F(5,2292) = 13.995, p < 0.01), birth volume (F(3,1864) = 8.35, p < 0.01), and patient acuity (F(2,2295) = 20.21, p < 0.01). When the practice environment was entered into the model with personal and practice characteristics, the explained variance increased from 6.4% to 26.5% (F(20,1478) = 27.98, p < 0.01).ConclusionsOur findings suggested that a key driver of burnout among US midwives was the practice environment, specifically practice leadership and participation and support for the midwifery model of care. Structural and personal characteristics contributed less to burnout score than the practice environment, implying that prevention of burnout may be achieved through organizational support and does not require structural changes to the provision of perinatal health.     

Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3–4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3–63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48–68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.     

Secondary cancer risk from modern external-beam radiotherapy of prostate cancer patients: Impact of fractionation and dose distribution

Modern radiotherapy (RT) uses altered fractionation, long beam-on time and image-guided procedure. This study aimed to compare secondary cancer risk (SCR) associated with primary field, scatter/leakage radiations and image-guided procedure in prostate treatment using intensity-modulated RT (IMRT), CyberKnife stereotactic body RT (CK-SBRT) in relative to 3-dimensional conformal RT (3D-CRT). Prostate plans were generated for 3D-CRT, IMRT (39 fractions of 2 Gy), and CK-SBRT (five fractions of 7.25 Gy). Excess absolute risk (EAR) was calculated for organs in the primary field using Schneider’s mechanistic model and concept of organ equivalent dose (OED) to account for dose inhomogeneity. Doses from image-guided procedure and scatter/leakage radiations were determined by phantom measurements. The results showed that hypofractionation relative to conventional fractionation yielded lower SCR for organs in primary field (p ≤ 0.0001). SCR was further modulated by dose-volume distribution. For organs near the field edge, like the rectum and pelvic bone, CK-SBRT plan rendered better risk profiles than IMRT and 3D-CRT because of the absence of volume peak in high dose region (relative risk [RR]: 0.65, 0.22, respectively, p ≤ 0.0004). CK-SBRT and IMRT generated more scatter/leakage and imaging doses than 3D-CRT (p ≤ 0.0002). But primary field was the major contributor to SCR. EAR estimates (risk contributions, primary field: scatter/leakage radiations: imaging procedure) were 7.1 excess cases per 10⁴ person–year (PY; 3.64:2.25:1) for CK-SBRT, 9.93 (7.32:2.33:1) for IMRT and 8.24 (15.99:2.35:1) for 3D-CRT (p ≤ 0.0002). We conclude that modern RT added more but small SCR from scatter/leakage and imaging doses. The primary field is a major contributor of risk which can be mitigated by the use of hypofractionation.     

Implantable cardiac pacemaker failure by cumulative dose effects of flattening filter free beams

Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter [WFF]) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects.     

Long-term clinical outcomes of patients receiving proton beam therapy for caudate lobe hepatocellular carcinoma

Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02) and a low serum alpha-fetoprotein level (AFP; P < 0.01) were significant factors predicting longer survival. The local control (LC) rates at one, three and five years were 100%, 85.9% and 85.9%, respectively, while the corresponding progression-free survival (PFS) rates were 65%, 27.5% and 22%, respectively. No grade 3 or worse adverse events were observed. PBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.     

Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy

The intention of this research was to define the predictive factors for acute esophagitis (AE) in lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy. The data for 72 lung cancer patients treated with concurrent chemoradiotherapy between 2008 and 2010 were prospectively evaluated. Mean lung dose, mean dose of esophagus, volume of esophagus irradiated and percentage of esophagus volume treated were analysed according to esophagitis grades. The mean esophageal dose was associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P < 0.001). However, the mean lung dose and the volume of esophagus irradiated were not associated with an increased risk of esophageal toxicity (Kruskal-Wallis test, P = 0.50 and P = 0.41, respectively). The mean radiation dose received by the esophagus was found to be highly correlated with the duration of Grade 2 esophagitis (Spearman test, r = 0.82, P < 0.001). The mean dose of esophagus ≥28 Gy showed statistical significance with respect to AE Grade 2 or worse (receiver operating characteristic curve analysis, 95% CI, 0.929–1.014). In conclusion, the mean esophageal dose was significantly associated with a risk of esophageal toxicity in patients with lung cancer treated with concurrent radiotherapy and chemotherapy.     

Prediction of post-radiotherapy survival for bone metastases: a comparison of the 3-variable number of risk factors model with the new Katagiri scoring system

We investigated patient survival after palliative radiotherapy for bone metastases while comparing the prognostic accuracies of the 3-variable number of risk factors (NRF) model and the new Katagiri scoring system (Katagiri score). Overall, 485 patients who received radiotherapy for bone metastases were grouped as per the NRF model (groups I, II and III) and Katagiri score (low-, intermediate- and high-risk). Survival was compared using the log-rank or log-rank trend test. Independent prognostic factors were identified using multivariate Cox regression analyses (MCRA). MCRA and receiver operating characteristic (ROC) curves were used to compare both models’ accuracy. For the 376 evaluable patients, the overall survival (OS) rates decreased significantly in the higher-tier groups of both models (P < 0.001). All evaluated factors except ‘previous chemotherapy status’ differed significantly between groups. Both models exhibited independent predictive power (P < 0.001). Per NRF model, hazard ratios (HRs) were 1.44 (P = 0.099) and 2.944 (P < 0.001), respectively, for groups II and III, relative to group I. Per Katagiri score, HRs for intermediate- and high-risk groups were 4.02 (P < 0.001) and 7.09 (P < 0.001), respectively, relative to the low-risk group. Areas under the curve (AUC) for predicting 6-, 18- and 24-month mortality were significantly higher when using the Katagiri score (P = 0.036, 0.039 and 0.022). Both models predict survival. Prognostic accuracy of the Katagiri score is superior, especially in patients with long-term survival potential; however, in patients with short prognosis, no difference occurred between both models; simplicity and patient burden should also be considered.     

A newly developed patient fixation system using a dedicated mouthpiece and dental impression materials for head and neck radiotherapy: a preliminary study

We evaluated the basic characteristics and efficacy of our newly developed patient fixation system for head and neck radiotherapy that uses a dedicated mouthpiece and dental impression materials. The present investigation demonstrated that with this system, the changes in the absorbed dose to water depending on the material of the mouthpiece were small, with a maximum of 0.32% for a 10-MV photon beam. For the dental impression material, we selected a silicone material with the lowest Hounsfield unit (HU) value that had little effect on the generation of artifacts and the quality of the X-ray beam. Multiphase magnetic resonance imaging (MRI) revealed that the head-up and -down motions in the thermoplastic shell without the mouthpiece were 5.76 ± 1.54 mm, whereas the motion with the mouthpiece decreased significantly to 1.72 ± 0.92 mm (P = 0.006). Similarly, the head-left and -right motion displacement decreased from 6.32 ± 1.86 mm without the mouthpiece to 1.80 ± 0.42 mm with the mouthpiece (P = 0.003). Regarding the tongue depressor function of the mouthpiece, the median distance from the hard palate to the surface of the tongue was 28.42 mm. The present results indicate that the new immobilization device developed herein that uses a mouthpiece and a thermoplastic shell is useful for suppressing patients’ head motions and tongue positions.     

A comparison of two visual inspection methods for cervical cancer screening among HIV-infected women in Kenya

Objective

To determine the optimal strategy for cervical cancer screening in women with human immunodeficiency virus (HIV) infection by comparing two strategies: visual inspection of the cervix with acetic acid (VIA) and VIA followed immediately by visual inspection with Lugol’s iodine (VIA/VILI) in women with a positive VIA result.

Methods

Data from a cervical cancer screening programme embedded in two HIV clinic sites in western Kenya were evaluated. Women at a central site underwent VIA, while women at a peripheral site underwent VIA/VILI. All women positive for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) on VIA and/or VILI had a confirmatory colposcopy, with a biopsy if necessary. Overall test positivity, positive predictive value (PPV) and the CIN 2+ detection rate were calculated for the two screening methods, with biopsy being the gold standard.

Findings

Between October 2007 and October 2010, 2338 women were screened with VIA and 1124 with VIA/VILI. In the VIA group, 26.4% of the women tested positive for CIN 2+; in the VIA/VILI group, 21.7% tested positive (P < 0.01). Histologically confirmed CIN 2+ was detected in 8.9% and 7.8% (P = 0.27) of women in the VIA and VIA/VILI groups, respectively. The PPV of VIA for biopsy-confirmed CIN 2+ in a single round of screening was 35.2%, compared with 38.2% for VIA/VILI (P = 0.41).

Conclusion

The absence of any differences between VIA and VIA/VILI in detection rates or PPV for CIN 2+ suggests that VIA, an easy testing procedure, can be used alone as a cervical cancer screening strategy in low-income settings.     

Household- and employment-related risk factors for depressive symptoms during the COVID-19 pandemic

ObjectivesThe COVID-19 pandemic has generated multiple psychological stressors, which may increase the prevalence of depressive symptoms. Utilizing Canadian survey data, this study assessed household- and employment-related risk factors for depressive symptoms during the pandemic.MethodsA sample of 1005 English-speaking Canadian adults aged 18+ years completed a web-based survey after physical distancing measures were implemented across Canada. Hierarchical binary logistic regression analyses were conducted to examine the associations of depressive symptoms with household- (household size, presence of children, residence locale) and employment-related (job with high risk of COVID-19 exposure, working from home, laid off/not working, financial worry) risk factors, controlling for demographic factors (gender, age, education, income).ResultsAbout 20.4% of the sample reported depressive symptoms at least 3 days per week. The odds of experiencing depressive symptoms 3+ days in the past week were higher among women (AOR = 1.67, p = 0.002) and younger adults (18–29 years AOR = 2.62, p < 0.001). After adjusting for demographic variables, the odds of experiencing depressive symptoms were higher in households with 4+ persons (AOR = 1.88, p = 0.01), in households with children aged 6 to 12 years (AOR = 1.98, p = 0.02), among those with a job at high risk for exposure to COVID-19 (AOR = 1.82, p = 0.01), and those experiencing financial worry due to COVID-19 (‘very worried’ AOR = 8.00, p < 0.001).ConclusionPandemic responses must include resources for mental health interventions. Additionally, further research is needed to track mental health trajectories and inform the development, targeting, and implementation of appropriate mental health prevention and treatment interventions.     

Dosimetric comparison between volumetric modulated arc therapy planning techniques for prostate cancer in the presence of intrafractional organ deformation

The purpose of this study was to compare single-arc (SA) and double-arc (DA) treatment plans, which are planning techniques often used in prostate cancer volumetric modulated arc therapy (VMAT), in the presence of intrafractional deformation (ID) to determine which technique is superior in terms of target dose coverage and sparing of the organs at risk (OARs). SA and DA plans were created for 27 patients with localized prostate cancer. ID was introduced to the clinical target volume (CTV), rectum and bladder to obtain blurred dose distributions using an in-house software. ID was based on the motion probability function of each structure voxel and the intrafractional motion of the respective organs. From the resultant blurred dose distributions of SA and DA plans, various parameters, including the tumor control probability, normal tissue complication probability, homogeneity index, conformity index, modulation complexity score for VMAT, dose–volume indices and monitor units (MUs), were evaluated to compare the two techniques. Statistical analysis showed that most CTV and rectum parameters were significantly larger for SA plans than for DA plans (P < 0.05). Furthermore, SA plans had fewer MUs and were less complex (P < 0.05). The significant differences observed had no clinical significance, indicating that both plans are comparable in terms of target and OAR dosimetry when ID is considered. The use of SA plans is recommended for prostate cancer VMAT because they can be delivered in shorter treatment times than DA plans, and therefore benefit the patients.     

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Analysis on the accuracy of CT-guided radioactive I-125 seed implantation with 3D printing template assistance in the treatment of thoracic malignant tumors

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p < 0.05). The mean values of all the errors of the chest wall cases were smaller than those of the lungs, and the differences were statistically significant (p < 0.05). There was no significant difference between the D90 calculated in the postoperative plan and those designed in the preoperative and intraoperative plans (p > 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p < 0.05). However, there were no statistical difference in the dosimetric parameters between the postoperative plans and intraoperative plans (p > 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation.     

Associations between estrogen receptor genetic polymorphisms,smoking status,and prostate cancer risk: a case–control study in Japanese men

Objective

Prostate cancer (PCa) is one of the major causes of death among men. Our study investigated the association of ESR1 and ESR2 genotypes with susceptibility to PCa in relation to smoking status in Japanese.

Method

A case–control study was performed with 750 Japanese prostate cancer patients and 870 healthy controls. After age-matching in case–controls, 352 controls and 352 cases were enrolled in this study. By using logistic regression analysis, the different genotypes from ESR1 and ESR2 were analyzed according to case/control status.

Result

ESR2 rs4986938 AG and AG + AA genotypes were associated with significantly decreased risk of PCa (AG: OR = 0.68, 95 % CI 0.47–0.97, P < 0.05 and AG + AA: OR = 0.67, 95 % CI 0.47–0.94, P < 0.05). However, there was no significant association between ESR1 rs2234693 and PCa risk. When patients were grouped according to smoking status, the ESR2 rs1256049 AA genotype (OR = 0.48, 95 % CI 0.25–0.95, P < 0.05) and ESR2 rs4986938 AG + AA genotype (OR = 0.64, 95 % CI 0.41–1.00, P < 0.05) showed significantly decreased PCa risk in the ever-smoker group.

Conclusion

Our results suggest that the estrogen receptor ESR2 has a very important function to predict PCa and that different SNPs have different predictive values. Smoking may influence estrogenic activity and may influence PCa together with the estrogen receptor.     

Comparing the toxicity and disease control rate of radiotherapy for prostate cancer between salvage settings after high-intensity focused ultrasound therapy and initial settings

The purpose of this retrospective study was to compare the toxicity and disease control rate of radiotherapy for prostate cancer in salvage settings after high-intensity focused ultrasound (HIFU) therapy (HIFU cohort) with those in radical settings (non-HIFU cohort). From 2012 to 2020, 215 patients were identified for this study and 17 were treated in the salvage settings after HIFU. The median follow-up time was 34.5 months (range: 7–102 months, inter-quartile range [IQR]: 16–64 months). Genitourinary (GU) and gastrointestinal (GI) adverse events were evaluated in acute and late periods with Common Terminology Criteria for Adverse Events version 5, and the rates of biochemical-clinical failure free survival (BCFS) and overall survival (OS) were estimated. The cumulative incidence of late GU Grade 2 or greater toxicity after five years was significantly different between the non-HIFU and HIFU cohorts with rates of 7.3% and 26.2%, respectively (P = 0.03). Regarding GI Grade 2 or greater toxicity, there was no significant difference between the two cohorts. The 5y-BCFS was 84.2% in the non-HIFU cohort and 69.5% in the HIFU cohort with no significant difference (P = 0.10) and the 5y-OS was 95.9% and 92.3%, respectively (P = 0.47). We concluded that the possibility of increased late GU Grade 2 or greater should be considered when applying salvage radiotherapy for local recurrence after HIFU.