Multiparametric magnetic resonance imaging (MRI)-based radiomics model explained by the Shapley Additive exPlanations (SHAP) method for predicting complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a multicenter retrospective study.

Background: Predicting the response to neoadjuvant chemoradiotherapy (nCRT) before initiating treatment is essential for tailoring therapeutic strategies and monitoring prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to develop and validate radiomic-based models to predict clinical and pathological complete responses (cCR and pCR, respectively) by incorporating the Shapley Additive exPlanations (SHAP) method for model interpretation. Methods: A total of 285 patients with complete pretreatment clinical characteristics and T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance imaging (MRI) at 3 centers were retrospectively recruited. The features of tumor lesions were extracted by PyRadiomics and selected using least absolute shrinkage and selection operator (LASSO) algorithm. The selected features were used to build multilayer perceptron (MLP) models alone or combined with clinical features. Area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were applied to evaluate performance of models. The SHAP method was adopted to explain the prediction models. Results: The radiomic-based models all showed better performances than clinical models. The clinical-radiomic models showed the best differentiation on cCR and pCR with mean AUCs of 0.718 and 0.810 in the validation set, respectively. The decision curves of the clinical-radiomic models showed its values in clinical application. The SHAP method powerfully interpreted the prediction models both at a holistic and individual levels. Conclusions: Our study highlights that the radiomic-based prediction models have more excellent abilities than clinical models and can effectively predict treatment response and optimize therapeutic strategies for patients with LARCs.

A Population-Based and Propensity Score-Matched Investigation of the Occurrence, Management, and Prognosis of Anal Mucinous Adenocarcinoma Patients.

INTRODUCTION: Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC. METHODS: We analyzed age-adjusted incidence (AAI) rates over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival. RESULTS: AAI of AMAC fluctuated within a narrow range (0.082-0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p = 0.348) and a better prognosis than AAC (p < 0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p < 0.05) and unmarried (p < 0.05) and somewhat less probably to need surgical removal (p < 0.01) and radiotherapy (p < 0.01). Elderly patients have lower rates of survival (p < 0.05). Localized stage was associated with better prognosis (p < 0.05). Surgery was associated with a tendency toward better survival (p = 0.095). CONCLUSIONS: AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend toward improved survival.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Suicide rates among patients with first and second primary cancer.

AIMS: With advancements in cancer treatments, the survival rates of patients with their first primary cancer (FPC) have increased, resulting in a rise in the number of patients with second primary cancer (SPC). However, there has been no assessment on the incidence of suicide among patients with SPC. This study assessed the occurrence of suicide among patients with SPC and compared them with that in patients with FPC. METHODS: This was a retrospective, population-based cohort study that followed patients with FPC and SPC diagnosed from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 17 registries database between 1 January 2000 and 31 December 2019. RESULTS: For patients with SPC, an age of 85+ years at diagnosis was associated with a higher incidence of suicide death (HR, 1.727; 95% CI, 1.075-2.774), while the suicide death was not considerably different in the chemotherapy group (P > 0.05). Female genital system cancers (HR, 3.042; 95% CI, 1.819-6.361) accounted for the highest suicide death among patients with SPC. The suicide death distribution of patients with SPC over time indicated that suicide events mainly occurred within 5 to 15 years of diagnosis. Compared with patients with FPC, patients with SPC in general had a lower risk of suicide, but increased year by year. CONCLUSION: The risk of suicide was reduced in patients with SPC compared with patients with FPC, but increased year by year. Therefore, oncologists and related health professionals need to provide continuous psychological support to reduce the incidence of suicide. The highest suicide death was found among patients with female genital system cancer.

Alternating Expiration and Inspiration Breath-Hold Spares the Chest Wall During Stereotactic Body Radiation Therapy for Peripheral Lung Malignancies.

PURPOSE: The proximity of tumors to the chest wall brings additional risks of chest wall pain during stereotactic body radiation therapy. Herein, we dosimetrically compared alternated breath-hold (ABH) plans with single BH plans and determined the common characteristics of eligible patients who may obtain better chest wall sparing using this technique. METHODS AND MATERIALS: Twenty patients with lung lesions adjacent to the chest wall were enrolled and received respiratory training. Their half-fraction end expiration BH and deep inspiration BH plans were summed to generate the ABH plans. Dosimetric parameters of the chest wall were compared between single and alternated BH plans, and the correlation between tumor location and the outcome of chest wall sparing was quantitatively evaluated. Pretreatment cone beam computed tomography variations in eligible patients were recorded as well. RESULTS: Compared with the end expiration BH and deep inspiration BH plans, the ABH plans reduced chest wall dosimetric results with median reductions of 2.0% and 3.9% (Dmax: maximum point dose), 15.4% and 14.8% (D1cc: dose to a volume of 1 cm3), and 48.8% and 63% (V30: volume receiving 30 Gy or more), respectively. Relative tumor displacements (ratio of tumor displacement in the superior-inferior direction to planning target volume diameter) were greater in the lower lobe than in the upper and middle lobes (1.17 vs 0.18). Meanwhile, better median reductions of 44% (Dmax), 46% (D1cc), and 98% (V30) were obtained in the lower lobe cohort using the ABH technique. Pretreatment variations for all BHs met the 5-mm threshold. CONCLUSIONS: The ABH technique can significantly spare the adjacent chest wall without compromising planning target volume coverage in comparison with the single BH, and patients with tumors in the lower lobes can obtain better chest wall sparing than in the upper and middle lobes. Further investigation is warranted to validate these findings.

An Ovarian Large-Cell Neuroendocrine Carcinoma Accompanied by Clear Cell Carcinoma with Specific High Level of AFP: Case Report and Review of the Literature.

Large cell neuroendocrine carcinoma (LCNEC) is a rare histological subtype of ovarian cancer. A few cases have been reported in the literature with extreme invasiveness and a poor prognosis. However, there still have not been accepted criteria for diagnosis and treatment of LCNEC. Here we report an unmarried 37 year-old woman who was diagnosed with LCNEC associated with clear cell carcinoma and the tumor index was manifested with a specific increase of AFP. The case received six courses of etoposide and carboplatin chemotherapy as an adjuvant therapy after primary curative surgery. However, she relapsed within 6 months after surgery and metastasized rapidly to distant organs despite combined chemotherapy of paclitaxel, cisplatin, and bevacizumab, and died 18 months after primary surgery. This is the first reported case of LCNEC manifested with a specific increase of AFP and characteristically metastasized to the spine as recurrence. Reviewing our case as well as previously reported cases, LCNEC present with aggressive malignancy and vulnerable to distant metastasis through a hematogenous approach, we conjectured that adding Bevacizumab in primary chemotherapy may be beneficial to extend disease-free survival. But so far there is no recommendation of this regimen for treatment of LCNEC in current guidelines. Further research is needed to confirm this view so as to find the best treatment of LCNEC and improve the prognosis of these patients.

Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer.

Background: Radiotherapy-associated secondary cancer is an important issue for the treatment of breast cancer (BCa). This study aimed to investigate the molecular mechanism and genetic risk factors for radiation-associated secondary diseases in BCa. Methods: The differentially expressed genes (DEGs) between preradiation and postradiation BCa samples in the GSE65505 dataset were obtained. The pathways related to the radiation-associated DEGs in the protein-protein interaction (PPI) network modules were identified. miRNAs targeted to the key genes in the PPI network were identified, and their association with BCa prognosis was analyzed. Results: A total of 136 radiation-associated DEGs preradiation and postradiation BCa samples were screened out. The PPI network consisted of a significant module that consisted of 21 upregulated DEGs that were associated with "hsa04512: ECM-receptor interaction," "hsa04151: PI3K-Akt signaling pathway," and "hsa04115: p53 signaling pathway." Sixteen DEGs, including three collagen genes collagen type I alpha 1 chain (COL1A1), COL3A1, and COL1A2, were enriched in 17 radiation-associated pathways. The three genes were upregulated in BCa tissues compared with controls and were also elevated by radiation. They were targeted by hsa-miR-29a/c, and the expression levels of hsa-miR-29a/c were associated with a poor prognosis of BCa. Conclusions: The upregulation of COL1A1, COL3A1, and COL1A2 might be genetic risk factors for radiation-associated secondary diseases in BCa.

Survival of Patients With Cervical Cancer Treated With Definitive Radiotherapy or Concurrent Chemoradiotherapy According to Histological Subtype: A Systematic Review and Meta-Analysis.

Background: Cervical cancer is a leading cause of morbidity and mortality for women worldwide. Different histopathological cervical cancer subtypes (i.e., adenocarcinoma/adenosquamous carcinoma, and squamous cell carcinoma) are all treated similarly with definitive radiotherapy or concurrent chemoradiotherapy, but studies have reported differing survival prognoses. In this review and meta-analysis, we compared the disease-free and overall survivals of patients with cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy according to the histopathological subtypes. Objective: To compare the disease-free and overall survivals of patients with adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy. Methods: We systematically searched the Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE academic databases following PRISMA guidelines. We identified publications to conduct a random-effects meta-analysis to evaluate the disease-free and overall survivals of patients with cervical adenocarcinoma/adenosquamous carcinoma and squamous cell carcinoma treated with definitive radiotherapy or concurrent chemoradiotherapy. Results: From 963 studies, we found eight eligible ones with 13,859 patients with cervical cancer (mean age, 52.2 ± 7.9 years). Our meta-analysis revealed a poorer outcome of disease-free (hazard ratio, 1.51; 95% CI, 1.28-1.79) and overall (hazard ratio 1.41; 95% CI, 1.26-1.57) survivals for patients with adenocarcinoma/adenosquamous carcinoma undergoing definitive radiotherapy or concurrent chemoradiotherapy than for those with squamous cell carcinoma undergoing similar treatments. We also observed that larger tumor size and advanced tumor stage are also significant prognostic factors that adversely impact survival outcomes in cervical cancer patients undergoing definitive radiotherapy or concurrent chemoradiotherapy. Conclusion: Our results show poor disease-free and overall survivals for patients with cervical cancer and adenocarcinoma/adenosquamous carcinoma than for those with squamous cell carcinoma after treatment with definitive radiotherapy or concurrent chemoradiotherapy. Our findings clarify the risks associated with the conventional management of cervical cancer according to the histological type.

Immobilization-assisted abdominal deep inspiration breath-hold in post-mastectomy radiotherapy of left-sided breast cancer with internal mammary chain coverage.

BACKGROUND: Whether to prophylactically irradiate the ipsilateral internal mammary chain (IMC) in post-mastectomy radiotherapy (PMRT) remains controversial because of equivocal clinical benefits against the added toxicities. Our previous study revealed that the cardiac dose was decreased during left-sided breast radiotherapy with abdominal deep inspiration breath-hold (aDIBH) as compared with free-breathing (FB) and thoracic deep inspiration breath-hold (tDIBH). Here we present the dosimetric advantage of aDIBH for patients undergoing PMRT with IMC coverage. METHODS: We prospectively analyzed 19 patients with left-sided breast cancer who underwent PMRT. Patients underwent computed tomography (CT) simulation under both free-breathing (FB) and aDIBH. The heart, left anterior descending coronary artery (LAD), lungs, and the contralateral breast was defined as organs at risk (OARs). Three-dimensional conformal radiation therapy (3D-CRT), inverse planning intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) were used to calculate the doses received by both the planning target volume (PTV) and OARs, which were compared using the Wilcoxon signed-rank test. RESULTS: Compared with FB, the Dmean of the heart and LAD were respectively reduced by 3.5 Gy (P<0.003) and 8.9 Gy (P<0.001) in 3D-CRT, 2.6 Gy (P<0.001), and 7.8 Gy (P=0.001) in IMRT, 1.5 Gy (P<0.001) and 4.5 Gy (P=0.001) in VMAT plans under aDIBH. Among all these plans, the Dmean of the heart was lowest in aDIBH IMRT and 1.3 Gy lower than in aDIBH VMAT (P=0.002). aDIBH IMRT also resulted in a significantly reduced dose to the ipsilateral lung than plans under FB (P<0.05). Dmean and V5 to the contralateral lung and breast were higher in VMAT plans (P<0.05). CONCLUSIONS: Using an immobilization-assisted aDIBH technique, radiation doses to the heart can be kept at reasonably low levels even if IMC is included in the clinical target volume (CTV). Among 3D-CRT, IMRT, and VMAT plans, IMRT plus aDIBH results in the best heart-sparing effect. We recommend that the aDIBH technique be routinely applied in suitable patients if the IMC is irradiated.

Impact of Lymphadenectomy on Outcomes of Early-Stage Ovarian Cancer: A Systematic Review and Meta-Analysis.

Objective: The study aimed to assess if additional lymphadenectomy with primary staging surgery improves overall survival (OS) and disease-free survival (DFS) of early-stage ovarian cancer (ESOC). Methods: PubMed and Embase databases were searched for any type of study comparing OS or DFS between lymphadenectomy and control groups for any type of ESOC. Adjusted hazard ratios (HR) were pooled in a random-effects model. Results: Twelve studies were included. Meta-analysis indicated that lymphadenectomy is associated with significantly improved OS only for epithelial tumors (HR 0.75 95% CI 0.68, 0.82 I2 = 0% p < 0.00001) but not for malignant germ cell tumors (HR 1.31 95% CI 0.88, 1.94 I2 = 0% p = 0.18). Single studies indicated a tendency of improved OS with lymphadenectomy which was significant for ovarian carcinosarcoma but not for sex cord-stromal tumors. On meta-regression of all histological types, the percentage of patients with lymph node metastasis in the lymphadenectomy group was not found to influence the effect size. Meta-analysis also indicated that lymphadenectomy is associated with significantly improved DFS for epithelial tumors (HR 0.59 95% CI 0.45, 0.77 I2 = 0% p < 0.0001). Single studies on malignant germ cell and sex cord-stromal tumors failed to demonstrate any significant beneficial effect of lymphadenectomy on DFS. Conclusions: Within the limitations of the review, lymphadenectomy may improve OS and DFS for epithelial ESOC. Scarce data suggest that lymphadenectomy is not associated with improved outcomes for malignant germ cell and sex cord-stromal tumors but may benefit ovarian carcinosarcoma. Large-scale RCTs and robust observational studies shall improve current evidence.

A mature cystic teratoma adherent to the vaginal wall: a case report.

We present the case of a woman diagnosed with a teratoma adherent to the vaginal wall. The patient had been misdiagnosed with an ovarian teratoma 8 years previously at her local hospital, but no mass was found in the pelvic cavity during cesarean section. She therefore attended our institution for further examination. Transvaginal ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT) revealed a large mass on the left side at the bottom of the pelvis, near the side of the vagina, mainly composed of greasy and cystic elements. Gynecological examination showed the mass protruding into the left side of the vaginal wall. The patient therefore underwent vaginal wall incision. During surgery, we found a mass adherent to the vaginal wall, located on the left front of the rectum. Surgery was completed successful with no complications. This case highlights the need for careful preoperative evaluation of teratomas with unusual locations. MRI and CT may be useful for identifying the origin of the tumor and determining its relationship with the surrounding tissues. Surgery should be based on the characteristics and anatomical location of the tumor to minimize damage to other tissues and organs.

The benefits evaluation of abdominal deep inspiration breath hold based on knowledge-based radiotherapy treatment planning for left-sided breast cancer.

PURPOSE: To study the impact of abdominal deep inspiration breath hold (DIBH) technique on knowledge-based radiotherapy treatment planning for left-sided breast cancer to guide the application of DIBH technology. MATERIALS AND METHODS: Two kernel density estimation (KDE) models were developed based on 40 left-sided breast cancer patients with two CT acquisitions of free breathing (FB-CT) and DIBH (DIBH-CT). Each KDE model was used to predict dose volume histograms (DVHs) based on DIBH-CT and FB-CT for another 10 new patients similar to our training datasets. The predicted DVHs were taken as a substitute for dose constraints and objective functions in the Eclipse treatment planning system, with the same requirements for the planning target volume (PTV). The mean doses to the heart, the left anterior descending coronary artery (LADCA) and the ipsilateral lung were evaluated and compared using the T-test among clinical plans, KDE predictions, and KDE plans. RESULTS: Our study demonstrated that the KDE model can generate deliverable simulations equivalent to clinically applicable plans. The T-test was applied to test the consistency hypothesis on another ten left-sided breast cancer patients. In cases of the same breathing status, there was no statistically significant difference between the predicted and the clinical plans for all clinically relevant DVH indices (P > 0.05), and all predicted DVHs can be transferred into deliverable plans. For DIBH-CT images, significant differences were observed between FB model predictions and clinical plans (P < 0.05). DIBH model prediction cannot be optimized to a deliverable plan based on FB-CT, with a counsel of perfection. CONCLUSION: KDE models can predict DVHs well for the same breathing conditions but degrade with different breathing conditions. The benefits of DIBH for a given patient can be evaluated with a quick comparison of prediction results of the two models before treatment planning.

Abdominal DIBH reduces the cardiac dose even further: a prospective analysis.

BACKGROUND: Deep inspiration breath hold (DIBH) can be performed using different breathing maneuvers, such as DIBH with a thoracic breathing maneuver (T-DIBH) and DIBH with an abdominal breathing maneuver (A-DIBH). Dosimetric benefits of A-DIBH were investigated in the treatment of left-sided breast cancer radiotherapy (RT) with both 3-Dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) techniques. METHODS: Twenty-two patients with left-sided breast cancer were enrolled in this study. 3D-CRT and IMRT plans were generated for each patient with three different CT scans of free breathing (FB), T-DIBH and A-DIBH. There were total of six treatment plans generated for each patient: FB_3D-CRT; TDIBH_3D-CRT; ADIBH_3D-CRT; FB-IMRT; TDIBH-IMRT; ADIBH-IMRT. Doses to the heart, left anterior descending coronary artery (LADCA), and ipsilateral lung were evaluated and compared using the Wilcoxon signed-rank test. RESULTS: The mean doses to the heart, LADCA and ipsilateral lung in 3D-CRT plans generated from 3D-CRT with FB, T-DIBH and A-DIBH were (2.89 ± 1.30), (1.67 ± 0.90) and (1.34 ± 0.43) Gy (all P < 0.05), respectively, with FB; (29.08 ± 16.72), (13.94 ± 14.74) and (10.22 ± 10.30) Gy (all P < 0.05), respectively, with T-DIBH; and (7.77 ± 2.71), (7.32 ± 1.42) and (6.90 ± 1.60) Gy (all P < 0.05), respectively, with A-DIBH. The mean doses to the heart, LADCA and ipsilateral lung in IMRT plans were generated from IMRT with FB, T-DIBH and A-DIBH were (1.96 ± 2.25), (1.37 ± 0.44) and (1.18 ± 0.26) Gy (all P < 0.05), respectively, with FB; (16.10 ± 7.45), (8.6 ± 6.60) and (7.35 ± 5.42) Gy (all P < 0.05), respectively, with T-DIBH; and (5.90 ± 2.24), (5.65 ± 1.58) and (5.62 ± 1.05) Gy (all P > 0.05), respectively, with A-DIBH. CONCLUSIONS: This study indicates that both 3D-CRT and IMRT plans with A-DIBH achieved lower cardiac and LADCA doses than plans with FB and T-DIBH; 3D-CRT plans with A-DIBH achieved lower ipsilateral lung doses than plans with FB and T-DIBH; and IMRT plans with A-DIBH had better outcomes than 3D-CRT plans with A-DIBH with respect to the mean dose to the heart, LADCA and ipsilateral lung. IMRT plans with A-DIBH should be incorporated into the daily routine for left-sided breast RT.