Impact of Varying Chest Wall Target Volume Delineation on Postmastectomy Radiation Therapy Outcomes in Breast Cancer Patients with Implant-Based Reconstruction.

BACKGROUND: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. METHODS: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. RESULTS: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. CONCLUSIONS: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.

Postchemoradiotherapy systemic inflammation response index predicts treatment response and overall survival for patients with locally advanced nasopharyngeal cancer.

BACKGROUND/PURPOSE: To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal cancer (NPC). METHODS: A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival. RESULTS: Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p = 0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p = 0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p = 0.017). CONCLUSION: The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol's chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

Orlistat Resensitizes Sorafenib-Resistance in Hepatocellular Carcinoma Cells through Modulating Metabolism.

Sorafenib is one of the options for advanced hepatocellular carcinoma treatment and has been shown to extend median overall survival. However, sorafenib resistance often develops a few months after treatment. Hence, developing various strategies to overcome sorafenib resistance and understand the possible mechanisms is urgently needed. We first established sorafenib-resistant hepatocellular carcinoma (HCC) cells. Then, we found that sorafenib-resistant Huh7 cells (Huh7/SR) exhibit higher glucose uptakes and express elevated fatty acid synthesis and glucose metabolism-related proteins than their parental counterparts (Huh7). The current study investigated whether sorafenib resistance could be reversed by suppressing fatty acid synthesis, using a fatty acid synthase (FASN) inhibitor, orlistat, in HCC cells. FASN inhibition-caused changes in protein expressions and cell cycle distribution were analyzed by Western blot and flow cytometry, and changes in glucose uptakes were also evaluated by 18F-FDG uptake. Orlistat remarkably enhanced the cytotoxicity of sorafenib in both Huh7 and Huh7/SR cells, and flow cytometry showed that combination treatment significantly increased the sub-G1 population in both cell lines. Western blot revealed that the combination treatment effectively increased the ratio of Bax/Bcl-2 and decreased expressions of pERK; additionally, the combination treatment also strongly suppressed fatty acid synthesis-related proteins (e.g., FASN and SCD) in both cell lines. Lastly, the 18F-FDG uptake was repressed by the combination treatment in both cell lines. Our results indicated that orlistat-mediated FASN inhibition could overcome sorafenib resistance and enhance cell killing in HCC by changing cell metabolism.

Cardiac Function after Modern Radiation Therapy with Volumetric Modulated Arc Therapy or Helical Tomotherapy for Advanced Left-Breast Cancer Receiving Regional Nodal Irradiation.

BACKGROUND: Protecting cardiac function in patients with advanced left-breast cancer receiving radiation therapy (RT) with regional nodal irradiation (RNI) is an important issue. Modern RT techniques can limit cardiac exposure. The aim of this study was to explore the association be-tween cardiac dose and cardiac function. METHODS: Between 2017 and 2020, we retrospectively reviewed left-breast cancer patients who received adjuvant RT, including RNI with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT). Left ventricular ejection fraction (LVEF) was assessed by echocardiography before RT and 1 year after RT to detect any early deterioration in cardiac systolic function. RESULTS: A total of 30 eligible patients were enrolled. The median follow-up time from the initiation of RT was 3.9 years (range 0.6-5 years). Seventeen patients received VMAT, and the other 13 patients received HT. The median RT dose was 55 Gray (Gy), and the mean heart dose was 3.73 Gy (range 1.95-9.36 Gy). The median LVEF before and after RT was 68% and 68.5%, respectively. No obvious deterioration was found. There was no association between cardiac dose (mean heart dose, V5-V30) and LVEF (change in values or post-RT). CONCLUSIONS: For left-breast cancer patients undergoing RT with RNI, VMAT, or HT can be used to limit cardiac exposure. Cardiac function as evaluated by LVEF revealed no obvious deterioration after RT in our patients, and no association was found between cardiac dose and LVEF in those treated with either VMAT or HT in early cardiac surveillance.

Cancer Detection Using an Artificial Secretable MicroRNA Found in Blood and Urine.

Biomarkers can potentially help in the detection and prognosis of diseases such as cancer, its recurrence, predicting response to therapy, and monitoring of response during and/or after treatment. Endogenous tumor blood biomarkers suffer from low concentrations that are not distinguishable from background noise and, if identified, the localization of the biomarker production site is not known. The use of exogenously introduced or artificial biomarkers can eliminate these issues. In this study, we show that cancer cells can be made to produce an artificial secreted microRNA (Sec-miR) that can be detected in media from cells in culture, and from both blood and urine in living mice. In culture, we show that chaining a number of Sec-miR sequences in a plasmid and transfecting cells with the plasmids could increase Sec-miR secretion as the number of sequences increases. Tumor induction in mice with a stably transfected HeLa cell line shows the presence and significant increase in the Sec-miR with time and tumor growth in plasma (p < 0.001, R2 = 0.5542). The relative half-life of the Sec-miR was seen to be 1.2 h in the plasma of living mice and was seen to appear in urine within 12 h. The transgene for the Sec-miR within a minicircle was introduced via the tail-vein into subcutaneous tumor-bearing mice. As the tumor growth increased with time, further in vivo transfection of the Sec-miR minicircles showed an increase in Sec-miR in both plasma and urine (R2 = 0.4546). This study demonstrated that an exogenous Sec-miR biomarker would allow for early tumor detection using in vitro diagnostics techniques.

Modern Rotational Radiation Techniques with Volumetric Modulated Arc Therapy or Helical Tomotherapy for Optimal Sparing of the Lung and Heart in Left-Breast Cancer Radiotherapy Plus Regional Nodal Irradiation: A Comparative Dosimetric Analysis.

BACKGROUND: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects patient outcomes. Modern arc RT techniques can improve normal organ sparing compared with conventional techniques. The aim of this study was to explore the optimal technique for left-breast RT with RNI. METHODS: We retrospectively reviewed patients receiving RT with RNI for left-breast cancer. We used modern arc RT techniques with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT) with a novel block technique, and compared differences in dosimetry parameters between the two groups. Subgroup analysis of RNI with or without internal mammary node (IMN) volume was also performed. RESULTS: A total of 108 eligible patients were enrolled between 2017 and 2020, of whom 70 received VMAT and 38 received HT. The median RT dose was 55 Gy. No significant differences were found regarding the surgery, RT dose, number of fractions, target volume, and RNI volume between the VMAT and HT groups. VMAT reduced the heart mean dose more than HT (3.82 vs. 5.13 Gy, p < 0.001), as well as the cardiac parameters of V5-V20, whole-lung mean dose, lung parameters of V5-V20, and contralateral-breast and esophagus mean dose. In the subgroup analysis of RNI with IMNs, the advantage of VMAT persisted in protecting the heart, lung, contralateral breast, and esophagus. HT was beneficial for lowering the thyroid mean dose. For RNI without IMN, VMAT improved the low-dose exposure of the heart and lung, but HT was similar to VMAT in terms of heart, whole-lung, and contralateral-breast mean dose. CONCLUSIONS: For patients with left-breast cancer receiving adjuvant RT with RNI, VMAT reduced the exposure dose to the heart, lung, contralateral breast, and esophagus compared with HT. VMAT was superior to HT in terms of normal organ sparing in the patients who underwent RNI with IMN irradiation. Considering the reduction in normal organ exposure and potential toxicity, VMAT is the optimal technique for patients receiving RNI when deep inspiration breath-hold is not available.

Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.

BladderScan Feedback Method in Predicting Bladder Filling for Prostate Radiotherapy: A Prospective Study.

PURPOSE: Approximately 5%-10% of men who receive prostate cancer radiotherapy will suffer from radiation cystitis. Bladder filling before the administration of radiotherapy results in lower radiation exposure to the bladder. BladderScan, an ultrasound-based bladder volume scanner, has the potential to evaluate bladder volume during radiotherapy; thus, a prospective pilot study was initiated. METHODS: Eleven men receiving tomotherapy for localized prostate cancer were enrolled. The validity of BladderScan was evaluated by comparing the measurements from BladderScan with the calculated volume from megavoltage computed tomography (MVCT). With a crossover design to compare different methods in bladder filling, the radiotherapy was divided into 2 sequences. Conventional method: the patient was asked to drink water after voiding urine. The amount of water and the duration of waiting were the same as in the setting of the simulation. BladderScan feedback method: the bladder filling procedure depended on the BladderScan measurements. RESULTS: There were 314 sets of data from 11 patients. The correlation coefficient between VBS and VCT was 0.87, where VBS is the mean volume of 3 measurements by BladderScan and VCT is the bladder volume derived from MVCT. The BladderScan feedback method resulted in a significant larger bladder volume than the conventional method, with a mean difference of 36.9 mL. When the failure was defined as VCT <80% of planned volume, the BladderScan feedback method brought about a relative reduction in the failure rate with an odds ratio of 0.44 and an absolute reduction of 9.1%. CONCLUSION: The accuracy of BladderScan was validated by MVCT in our study. The BladderScan feedback method can help patients fill the bladder adequately, with a larger bladder volume and a lower failure rate.

Elevation of CD109 promotes metastasis and drug resistance in lung cancer via activation of EGFR-AKT-mTOR signaling.

Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer-related deaths. Thus, understanding the mechanism of lung cancer metastasis will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF-elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.

Prophylactic NS-21 maintains the skin moisture but does not reduce the severity of radiation dermatitis in patients with head and neck cancer: a randomized control trial.

BACKGROUND: To evaluate the practicality of NS-21 cream with regard to its skin-related toxicity in patients with head and neck cancer (HNC) who are undergoing concurrent chemoradiation therapy (CCRT) or radiotherapy (RT). METHODS: Between July 2015 and November 2017, 30 HNC patients who underwent RT or CCRT were randomly allocated to receive either NS-21 or control treatment on their irradiated skin three times per day, starting at the initiation of RT or CCRT and ending 2 weeks after the completion of RT or until the appearance of grade 3 acute radiation dermatitis (ARD). Dermatitis was recorded weekly according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Skin humidity was monitored by a digital moisture meter. The generalized estimating equation (GEE) and logit link function method were used for statistical analysis. RESULTS: No serious adverse events were observed in either group. Itching dermatitis occurred on the right lower neck in one patient of the NS-21 group during the 3rd week of CCRT, but the severity was mild. The median skin moisture value at the time of the final treatment was significantly different between the study and control groups (30.6 vs. 27.3, p = 0.013). Additionally, there was an inverse relationship between skin moisture and ARD grade (B = -0.04, p = 0.005). The incidence of ARD at the time of the last treatment was not significantly different between the study and control groups (6.7% vs 26.7%, p = 0.165). The risk of grade 3 ARD for skin that had received an irradiation dose of 47-70 Gy was higher than that of skin that had received an irradiation dose ≤46 Gy (OR = 31.06, 95% CI =5.95-162.21, p < 0.001). Nevertheless, the risk of ARD was not significantly different between the groups (OR = 0.38, 95% CI = 0.08-1.74, p = 0.212). CONCLUSIONS: NS-21 was well tolerated and effective for the maintenance of skin moisture; however, there was no statistically significant reduction in the risk of ARD in HNC patients undergoing RT or CCRT when compared with HNC patients in the control group. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Far Eastern Memorial Hospital ( FEMH-IRB , 104048-F), Registered 1st June 2015.

Esophageal Metal Stents with Concurrent Chemoradiation Therapy for Locally Advanced Esophageal Cancer: Safe or Not?

BACKGROUND: The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self-expandable metal stents (SEMS) for the treatment of locally advanced esophageal cancer. MATERIALS AND METHODS: Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty-eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed. RESULTS: The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio [HR], 72.30; 95% confidence interval [CI], 8.62-606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15-15.21; p < .001). CONCLUSION: CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life-threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations. IMPLICATIONS FOR PRACTICE: Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.

Unusual axillary metastasis of recurrent nasopharyngeal cancer: A case report.

RATIONALE: Nasopharyngeal carcinoma (NPC) has a high propensity of metastasis. The most commonly described sites of distant metastasis are the bones, lungs, and liver, whereas axillary metastasis is seldom reported. PATIENT CONCERNS: We hereby present the case of a 66-year-old man with NPC, cT2N2M0, at diagnosis. He had completed chemoradiotherapy and been disease-free for 7 years. DIAGNOSES: After that period, late recurrence in the form of a solitary axillary lymph node metastasis was detected and confirmed by core-needle biopsy. INTERVENTIONS: The lesion was chemoresistant but responded to salvage radiotherapy at a dose of 65 Gy in 21 fractions. OUTCOMES: Post-radiotherapy positron emission tomography scan showed no evidence of disease. LESSONS: We suggested that long-term follow-up of NPC patients is important because a late relapse may occur at an unusual site. Aggressive management of solitary metastasis may achieve good outcome.

Recall radiation dermatitis by sorafenib following stereotactic body radiation therapy.

We report on a 63-year-old man with a history of hepatitis B virus-related hepatocellular carcinoma with a thrombus extending into the inferior vena cava, who received image-guided stereotactic body radiation therapy (SBRT) with helical tomotherapy, followed by sorafenib. A total tumor dose of 48 Gy was delivered by 6 fractions within 2 weeks. The tumor responded dramatically, and the patient tolerated the courses well. Ten days after SBRT, sorafenib (200 mg), at 1.5 tablets twice a day, was prescribed. One week later, grade 2 recall radiation dermatitis subsequently developed in the previous SBRT off-target area. SBRT followed by sorafenib for the treatment of a portal vein thrombosis provided effective results, but the potential risk of enhanced adverse effects between radiation and sorafenib should be considered with caution, especially under a SBRT scheme.