Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

BACKGROUND: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. METHODS: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). RESULTS: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). CONCLUSION: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

Dosimetric characteristics of self-expandable metallic and plastic stents for transpapillary biliary decompression in external beam radiotherapy.

There is little evidence regarding radiation dose perturbation caused by the self-expandable metallic stents (SEMSs) used for transpapillary biliary decompression. We aimed to compare SEMSs with plastic stents (PSs) and clarify their dosimetric characteristics. Fifteen SEMSs (10 braided and 5 lasercut type) and six PSs (diameter: 2.3-3.3 mm) were inserted into a water-equivalent solid phantom. In total, 13 SEMSs had radiopaque markers, whereas the other two did not. Using radiochromic films, the dose difference adjacent to the stents at locations proximal, distal, and arc delivery to the radiation source was evaluated based on comparison to measurement of the dose delivery in phantom without any stent in place. The median values of the dose difference for each stent were used to compare the SEMS and PS groups.Results: The dose difference (median (minimum/maximum)) was as follows: proximal, SEMSs + 2.1% (1.8 / 4.7) / PSs + 5.4% (4.1 / 6.3) (p < 0.001); distal, SEMSs -1.0% (-1.6 /-0.4) / PSs -8.9% (-11.7 / -7.4) (p < 0.001); arc delivery, SEMSs 1.2% (0.9 / 2.3) / PSs 2.2% (1.6 / 3.6) (p = 0.005). These results demonstrated that the dose differences of SEMSs were significantly smaller than those of PSs. On the other hand, the dose difference was large at surface of the radiopaque markers for SEMSs: proximal, 10.3% (7.2 / 20.9); distal, -8.4% (-16.3 / -4.2); arc delivery, 5.5% (4.2 / 9.2). SEMSs for biliary decompression can be safely used in patients undergoing radiotherapy, by focusing on the dose distribution around the stents and by paying attention to local changes in the dose distribution of radiopaque markers.

Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement.

BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

Live birth from ovarian grafted tissue after pelvic radiation for rectal cancer.

Objective: To study the management of a woman who returned to conceive after high-dose radiation treatment, with documentation of uterine dosimetry, and the efficacy of ovarian tissue grafted into an irradiated pelvis. Design: Case report. Setting: Private and public In Vitro Fertilization units. Patient: A 26-year-old woman underwent radiation treatment for rectal cancer, with half of the uterus and the fundus being exposed to radiation doses of 50 and 25 Gy, respectively. We report the details of the uterine assessment, determining suitability of conception with her own uterus, pregnancy surveillance, and reproductive outcome. Interventions: In Vitro Fertilization stimulation grafted ovarian tissue to assist with pregnancy. Main Outcome Measures: Successful conception and live birth, pregnancy complications and management of high risk pregnancy. Results: The results of magnetic resonance imaging and pelvic ultrasound showed a small uterus with preserved junctional zone anatomy, and although the endometrium was initially thin after high-dose estrogen administration, endometrial thickness increased with time. Twelve grafted ovarian tissue stimulation cycles led to 4 embryo transfers, the last of which resulted in a live birth. She had 2 cervical cerclage procedures because of cervical shortening and delivered a 3.3-kg healthy female neonate at 38 weeks of gestation via lower-segment cesarean section. Conclusions: Successful pregnancy is possible from ovarian tissue grafted into an irradiated pelvis, with high-dose uterine exposure. Careful uterine assessment needs to be undertaken to determine suitability of conception attempt with a patient's own uterus, in consultation with the medical team. Further studies are needed to correlate imaging and biopsy findings with reproductive outcomes.

FAM20A: a potential diagnostic biomarker for lung squamous cell carcinoma.

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC. Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, and TIMER database, were employed to assess the diagnostic and prognostic value of FAM20A in LUSC. These tools also helped evaluate immune cell infiltration, immune checkpoint genes, DNA repair-related genes, DNA methylation, and tumor-related pathways. Results: FAM20A expression was found to be significantly reduced in LUSC, correlating with lower survival rates. It exhibited a negative correlation with key proteins in DNA repair signaling pathways, potentially contributing to LUSC's radiotherapy resistance. Additionally, FAM20A showed a positive correlation with immune checkpoints like CTLA-4, indicating potential heightened sensitivity to immunotherapies targeting these checkpoints. Conclusion: FAM20A emerges as a promising diagnostic and prognostic biomarker for LUSC, offering potential clinical applications.

Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review.

BACKGROUND: Natural compounds such as Berberine (Ber) have been considered due to favorable anticancer properties, low side effects, and availability along with chemotherapy treatments. OBJECTIVES: This study aimed to investigate the radiosensitizing and radioprotective properties of Ber. METHODS: In this systematic review that was performed according to PRISMA 2020 guidelines, we searched the publications before 25 Sep 2023 in Web of Science, PubMed, Scopus, Embase, and Cochrane Library databases. After determining inclusion and exclusion criteria, data were extracted and imported into an Excel form, and the results of the studies were reviewed. RESULTS: Ber by reducing the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-ß1), and increasing interleukin 10 (IL-10) levels, showed its antioxidant and anti-inflammatory properties against ionizing radiation. Reducing cell cytotoxicity and apoptosis were other radioprotective properties of Ber. Conversely, in cancer cells, Ber, via inducing oxidative stress and accumulation ROS in tumor tissues, inducing DNA damage, mitochondrial dysfunction and hyperpolarization, inducing apoptosis, and cell cycle arrest, inhibits the up-regulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) revealed radiosensitizing properties. CONCLUSION: Ber, via various mechanisms, showed favorable radioprotective and radiosensitizing properties in clinical and experimental studies. However, more clinical studies are needed in this field.

A retrospective study on the impact of radiotherapy on the survival outcomes of small cell lung cancer patients based on the SEER database.

Small cell lung cancer (SCLC) patients exhibit significant heterogeneity in tumor burden, physical condition, and responses to initial treatment. This diversity in treatment responses can result in varying treatment outcomes. The primary objective of this study was to explore the patient demographics associated with improved survival outcomes through radiotherapy. Based on the SEER database, we identified 42,824 SCLC patients enrolled between 2004 and 2015. These patients were stratified into radiotherapy (n = 20,360) and non-radiotherapy groups (n = 22,464). We controlled for confounding factors using propensity score matching (PSM) analysis. Subsequently, Kaplan-Meier (KM) analysis was employed to evaluate the impact of radiotherapy on patients' overall survival (OS) and cancer-specific survival (CSS). Cancer-specific mortality was further analyzed using competitive risk models. Cox analysis was also conducted to examine additional variables potentially affecting the survival of SCLC patients. We identified a total of 42,824 eligible patients, and following PSM, 13,329 patients were successfully matched in both the radiotherapy and non-radiotherapy groups. The KM analysis showed that the median OS was 9 months in the radiotherapy group and 6 months in the non-radiotherapy group. The median CSS was 10 months in the radiotherapy group and 7 months in the non-radiotherapy group. The 5-year OS and 10-year OS rates were 6.2% versus 1.6% in the radiotherapy group and 2.6% versus 0.8% in the non-radiotherapy group (P < 0.001). Competitive risk analysis showed that cancer-specific mortality was significantly higher in the non-radiotherapy group than in the radiotherapy group (P < 0.001). Multivariate Cox analysis showed that the radiotherapy group (relative non-radiotherapy group) showed a significant positive effect on survival outcomes (OS: HR 0.658 95% CI [0.642, 0.675] P < 0.001; CSS: HR 0.662 95% CI [0.645, 0.679], P < 0.001). In addition, age, gender, race, primary tumor site, T stage, N stage, M stage, chemotherapy, and surgery were also considered as important predictors of SCLC outcome. The results of the subgroup analysis showed that the radiotherapy group showed a significant survival advantage regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery (P < 0.001). Radiotherapy may improve both OS and CSS in SCLC patients. Patients with SCLC may benefit from radiotherapy regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery.

Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.

BACKGROUND: The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks. METHODS: Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification-mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC. RESULTS: We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT). CONCLUSIONS: Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.

Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

BACKGROUND: The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. METHODS: A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. RESULTS: The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma in situ. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. CONCLUSIONS: The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study.

BACKGROUND AND OBJECTIVE: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. METHODS: A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. KEY FINDINGS AND LIMITATIONS: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. PATIENT SUMMARY: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

Real-world implementation of North American and SIOP strategies for the treatment of Wilms tumor in Uruguay.

Wilms tumor has been selected as an index tumor by the WHO Global Initiative for Childhood Cancer with the aim to improve cure rates worldwide. Nevertheless, there is a scarcity of published data on outcomes beyond those of the major cooperative groups. Therefore, we conducted a retrospective analysis including all patients with Wilms tumor treated at our referral center in Uruguay between 1995 and 2020. Treatment consisted of North American (NA) strategies in 23 cases (1995-2004), followed by the SIOP strategy in 35 cases thereafter. Staging included: I-II = 28, III = 7, IV = 14, and V = 9. There were no major surgical or medical complications; however, a delay in the administration of local radiotherapy was observed (median of 21 days after surgery). There were no cases of toxicity- or surgery-related deaths or treatment abandonment. Five-year probability of overall survival was 0.72 and 0.92 for the NA and SIOP groups, respectively. We conclude that outcomes were better for the SIOP strategy with no unexpected toxicities and high treatment compliance in both strategies. Timely implementation of radiotherapy was challenging.

The impact of different modalities of chemoradiation therapy and chemotherapy regimens on lymphopenia in patients with locally advanced non-small cell lung cancer.

Background: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT. Methods: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×103 cells/µL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination. Results: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1). Conclusions: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.

Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.

Ferroptosis is a type of cell death that relies on iron and is distinguished by the occurrence of lipid peroxidation and the buildup of reactive oxygen species. Ferroptosis has been demonstrated to have a significant impact on the advancement and resistance to treatment of hepatocellular carcinoma (HCC), thereby highlighting its potential as a viable therapeutic target. Ferroptosis was observed in HCC tissues in contrast to normal liver tissue. The inhibition of ferroptosis has been found to increase the viability of HCC cells and decrease their susceptibility to various anticancer therapies, including chemotherapy, radiotherapy, and immune checkpoint blockade. The administration of drugs that directly modulate ferroptosis regulators or induce excessive production of lipid-reactive oxygen species has demonstrated the potential to enhance the responsiveness of drug-resistant HCC cells to treatment. However, the precise mechanism underlying this phenomenon remains ambiguous. This review presents a comprehensive overview of the crucial role played by ferroptosis in enhancing the efficacy of treatment for hepatocellular carcinoma (HCC). The main aim of this study is to examine the feasibility of utilizing ferroptosis as a therapeutic approach to improve the efficacy of HCC treatment and overcome drug resistance.

Thrombocytopenia and hyperprogression after radiotherapy and camrelizumab treatment in an esophageal cancer patient with increased JAK2 gene copies: a case report.

Radiotherapy (RT) and immune checkpoint inhibitor (ICI) are important treatments for esophageal cancer. Some studies have confirmed the safety and effectiveness of using RT in combination with ICI, while serious side effects have been exhibited by some patients. We report a patient with metastatic esophageal cancer who received RT combined with ICI. The patient experienced severe thrombocytopenia, and treatment with thrombopoietin and corticosteroids were ineffective. Finally, the patient developed abscopal hyperprogression outside the radiation field. Interestingly, next-generation sequencing revealed increased JAK2 gene copies in the surgical slices. The JAK2/STAT3 pathway is involved in the regulation of megakaryocyte development. Recurrent thrombocytopenia may activate the JAK2/STAT3 pathway, leading to megakaryocyte differentiation and platelet biogenesis. However, persistent activation of the JAK2/STAT3 pathway has been associated with immune ICI resistance and tumor progression. This case indicates that thrombocytopenia and increased JAK2 gene copies may be risk factors for poor prognosis after ICI and RT treatment.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

Systemic Candida abscess after hypofractionated radiotherapy with temozolomide for glioblastoma in an older patient: illustrative case.

BACKGROUND: Hypofractionated radiotherapy with temozolomide is recommended for older patients with glioblastoma. Nevertheless, a potential complication of treatment is opportunistic infections with immunosuppression. OBSERVATIONS: An 86-year-old man presented with hemiparesis, prompting an investigation that revealed a right frontotemporal glioblastoma, isocitrate dehydrogenase wildtype. After the diagnostic biopsy, hypofractionated radiotherapy with temozolomide was administered. Lymphocytopenia was observed before the start of chemoradiotherapy and gradually worsened until 2 months later, possibly as a side effect of the treatment. One month after the completion of the initial treatment, the patient developed septic shock, leading to death within 2 days. Postmortem examination with autopsy revealed evidence of an invasive Candida infection possibly originating from the urinary catheter. LESSONS: Immunodeficiency, which is a side effect of radiation therapy with temozolomide, can cause rare and potentially fatal invasive Candida infections, especially in older and frail patients with newly diagnosed glioblastoma, even with short-term hypofractionated chemoradiotherapy. https://thejns.org/doi/10.3171/CASE24175.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Pan-cell death-related signature reveals tumor immune microenvironment and optimizes personalized therapy alternations in lung adenocarcinoma.

This study constructed a comprehensive analysis of cell death modules in eliminating aberrant cells and remodeling tumor microenvironment (TME). Consensus analysis was performed in 490 lung adenocarcinoma (LUAD) patients based on 4 types of cell death prognostic genes. Intersection method divided these LUAD samples into 5 cell death risk (CDR) clusters, and COX regression analysis were used to construct the CDR signature (CDRSig) with risk scores. Significant differences of TME phenotypes, clinical factors, genome variations, radiosensitivity and immunotherapy sensitivity were observed in different CDR clusters. Patients with higher risk scores in the CDRSig tended to be immune-excluded or immune-desert, and those with lower risk scores were more sensitive to radiotherapy and immunotherapy. The results from mouse model showed that intense expression of the high-risk gene PFKP was associated with low CD8+ T cell infiltration upon radiotherapy and anti-PD-L1 treatment. Deficient assays in vitro confirmed that PFKP downregulation enhanced cGAS/STING pathway activation and radiosensitivity in LUAD cells. In conclusion, our studies originally performed a comprehensive cell death analysis, suggesting the importance of CDR patterns in reprogramming TME and providing novel clues for LUAD personalized therapies.

Development and validation of an automated Tomotherapy planning method for cervical cancer.

PURPOSE: This study aimed to develop an automated Tomotherapy (TOMO) planning method for cervical cancer treatment, and to validate its feasibility and effectiveness. MATERIALS AND METHODS: The study enrolled 30 cervical cancer patients treated with TOMO at our center. Utilizing scripting and Python environment within the RayStation (RaySearch Labs, Sweden) treatment planning system (TPS), we developed automated planning methods for TOMO and volumetric modulated arc therapy (VMAT) techniques. The clinical manual TOMO (M-TOMO) plans for the 30 patients were re-optimized using automated planning scripts for both TOMO and VMAT, creating automated TOMO (A-TOMO) and automated VMAT (A-VMAT) plans. We compared A-TOMO with M-TOMO and A-VMAT plans. The primary evaluated relevant dosimetric parameters and treatment plan efficiency were assessed using the two-sided Wilcoxon signed-rank test for statistical analysis, with a P-value < 0.05 indicating statistical significance. RESULTS: A-TOMO plans maintained similar target dose uniformity compared to M-TOMO plans, with improvements in target conformity and faster dose drop-off outside the target, and demonstrated significant statistical differences (P+ < 0.01). A-TOMO plans also significantly outperformed M-TOMO plans in reducing V50Gy, V40Gy and Dmean for the bladder and rectum, as well as Dmean for the bowel bag, femoral heads, and kidneys (all P+ < 0.05). Additionally, A-TOMO plans demonstrated better consistency in plan quality. Furthermore, the quality of A-TOMO plans was comparable to or superior than A-VMAT plans. In terms of efficiency, A-TOMO significantly reduced the time required for treatment planning to approximately 20 min. CONCLUSION: We have successfully developed an A-TOMO planning method for cervical cancer. Compared to M-TOMO plans, A-TOMO plans improved target conformity and reduced radiation dose to OARs. Additionally, the quality of A-TOMO plans was on par with or surpasses that of A-VMAT plans. The A-TOMO planning method significantly improved the efficiency of treatment planning.