Combined Modality Research Articles

A systematic review and meta-analysis of efficacy, safety, and satisfaction rates of laser combination treatments vs laser monotherapy in skin rejuvenation resurfacing.

Laser therapies have been well-established in ameliorating skin-aging consequences. This systematic review aims to determine the efficacy, safety profile, and satisfaction rates of laser combination therapies on skin rejuvenation resurfacing. A systematic search was performed in four major databases up to September 2022. Skin rejuvenation studies were eligible comprising at least one laser combination arm, inclusive of all laser types (ablative or non-ablatives), and one monotherapy arm selected from one of the combined modalities. Studies combining one laser modality with radiofrequency (RF) or intense pulse light (IPL) were also assessed. Trials that did not encompass a monotherapy control arm were evaluated independently as single-arm studies. Eighteen clinical trials recruiting 448 cases were included after screening. A total of 532nm KTP + 1064nm Nd:YAG and 2940nm Er:YAG + Nd:YAG were the two most utilized laser combinations and exerted higher improvements and milder adverse events, compared to their monotherapy in most studies. Combining CO2 with rhodamine-IPL or gallium arsenide laser increased efficacy and satisfaction and brings about faster skin recovery time. Augmenting CO2 + RF did not increase improvement vs CO2 laser alone but prolonged skin erythema. Our meta-analysis revealed the pooled prevalence of quartile improvement rates as 0%, 28%, 40%, 27% in laser combination group, and 0%, 9%, 31%, 17% in laser monotherapy group, respectively. The satisfaction within each quartile category was 39%, 25%, 15%, 7% in laser combination and 20%, 25%, 16%, 17% in laser monotherapy, respectively, suggestive of the higher efficacy and satisfaction of laser combination group. The pain scores were lower in laser combination group than monotherapy (4.8 ± 1.18 vs 7.18 ± 0.7, converted on a scale of 0 to 10). Post-laser skin erythema lasted less longer in the combination group (12.8 vs 15.24days). Laser combination therapies were discovered to be superior to their monotherapies in terms of clinical improvement rates, diminished adverse events such as pain and erythema and patients satisfaction rates. Due to paucity of high-quality reportings, additional trials are warranted to corroborate these results.

Treatment Outcomes of Concurrent Nimotuzumab with Intensity Modulated Radiotherapy in Advanced Nasopharyngeal Carcinoma Patients Unfit for Concurrent Chemoradiotherapy: A Single Institute Experience

To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) combined with nimotuzumab for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) medically unfit to receive concomitant chemotherapy. From 2016.6 to 2020.9, 34 newly diagnosed patients with local-regional advanced NPC medically unfit for concurrent chemoradiation had undergone definitive radiotherapy and were retrospectively evaluated. All patients were treated with IMRT combined treatment modality of nimotuzumab with or without cisplatin-based induction chemotherapy. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Acute and late radiation-related toxicities were evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 during and after IMRT. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate prognostic analyses were performed by using the Cox proportional hazard model. The median follow-up time for the entire group was 15 months (range 5 to 55 months). At the time of this analysis, a total of 2 cases developed loco-regional recurrence. In addition, 4 patients developed distant metastasis. There was a total of 5 deaths: 3 patients died from distant metastasis, 1 patient died from the progression of loco-regional disease after recurrence, and the causes of death for the additional 1 case was a nasopharyngeal ulcer and deadly bleeding. The 1-year OS rate of the whole cohort was 87.9%, and the 1-year LFFR, DFFR, and PFS rates were 100%, 91.0%, and 91.0%, respectively. During the period of concurrent nimotuzumab and IMRT, no grade 3-4 hematologic toxicities and dermatitis were observed. Grade 3-4 radiotherapy-related oral mucositis was reported in 7 patients (20.6%). No infusion reaction was observed. No acneiform eruptions were found among these patients. The most commonly observed late complication was xerostomia. The degree of dry mouth in most patients was mild-to-moderate at the time of the last follow-up. Finally, 7 patients developed either unilateral or bilateral hearing impairment. One female patient experienced a nasopharyngeal ulcer and deadly bleeding after 5 months of completion of radiotherapy. Concurrent nimotuzumab with IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC medically unfit for concomitant chemotherapy. Further clinical trials are needed to confirm these findings.

Radiotherapy Effect on Long-Term Net Survival Benefit for Early-Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era

It is controversial whether to add consolidative radiotherapy (RT) after chemoimmunotherapy in the first-line treatment for diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the long-term net survival benefit of RT for early-stage DLBCL in the rituximab era. The data of 10,841 adult patients with early-stage DLBCL from the Surveillance, Epidemiology, and End Results (SEER) database between 2002 and 2015 were extracted and analyzed. The patients had received combined modality treatment (CMT, chemotherapy plus RT) or chemotherapy alone. Linear regression analysis was performed for RT utilization by year of diagnosis. Competing risk analysis was used to evaluate the cumulative incidence of mortality according to the cause of death. Inverse probability of treatment weighting (IPTW) was used to balance the distribution of covariates between treatment arms. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were performed to estimate the net survival benefit of RT by controlling for background mortality. Linear regression revealed that the slope of the best-fit line for RT utilization over time was negative between 2002 and 2015 (m = -0.006, P = 0.003). A total of 4,648 deaths were recorded among 10,841 patients; 55.6% were lymphoma-related death (LRD), and 44.4% were attributed to other causes. Patients initially treated with CMT had a lower cumulative incidence of LRD than chemotherapy alone (HR 0.63, 95% CI: 0.57-0.69; P < 0.001). The 10-year overall survival (OS) rate of 66.1%, RS rate of 85.0%, and SMR of 1.71 achieved with CMT were significantly better than chemotherapy alone (OS, 53.0%; RS, 69.8%; SMR, 2.62; P < 0.001). By IPTW and multivariable analysis, the addition of RT remained associated with better OS (HR 0.67, 95% CI: 0.62-0.71; P < 0.001) and RS (HR 0.69, 95% CI: 0.65-0.74; P < 0.001). RT was associated with better long-term net survival in patients with early-stage DLBCL in the rituximab era.

Relationship of Sarcopenia to Tolerance of Chemotherapy During Definitive Treatment of Primary Anal Squamous Cell Carcinoma

Primary therapy for anal squamous cell carcinoma consists of definitive radiation with concurrent chemotherapy, most commonly 5-fluorouracil and mitomycin-C. This regimen is associated with significant cutaneous, hematologic, and gastrointestinal toxicity. Sarcopenia, or low skeletal muscle mass, has been described as an adverse prognostic factor and predictor of poor tolerance to therapy across a range of malignancies, including breast, gynecologic and head and neck cancers. Here, we sought to determine if the presence of sarcopenia at the initiation of therapy is associated with increased rates of toxicity and poorer tolerance of definitive treatment for primary anal squamous cell carcinoma. This was a review of patients treated with curative intent for anal squamous cell carcinoma at a single academic medical center between 2007 and 2017, median follow up was 38 months. Analysis was limited to patients receiving definitive radiation with concurrent chemotherapy. Sarcopenia was objectively defined, using previously validated methods, as a skeletal muscle index (SMI) <41 cm2/m2 for female patients regardless of body mass index (BMI); for male patients sarcopenia was defined as SMI<43cm2/m2 for BMI<25 and <53 cm2/m2 for BMI >25. SMI calculations were performed using the average skeletal muscle cross sectional areas of two sequential axial CT slices at the L3 vertebral level obtained from radiation planning computed tomography scans. The image analysis was performed by a single trained observer using Sliceomatic software with a Hounsfield unit threshold of -29 to 150 to define skeletal muscle. Sarcopenia as a predictor for treatment toxicity was analyzed using Chi-Square testing. Overall survival and progression free survival were compared with 2-sample t tests. Sixty-one patients were included in the analysis with 49% meeting criteria for sarcopenia. Stage did not differ although sarcopenic patients were significantly more elderly than those without sarcopenia (mean 72 vs 58 years, p<0.001). Patients with sarcopenia were significantly more likely to have chemotherapy breaks, chemotherapy dose reductions, and incomplete chemotherapy courses compared to non-sarcopenic patients (33.3% vs 9.7%; p = 0.02). Sarcopenia was not predictive of more radiation treatment breaks, hematologic toxicity, progression free survival or overall survival. Sarcopenia is predictive of reduced tolerance to chemotherapy among patients receiving definitive combined modality therapy for primary anal carcinoma. We found no association between sarcopenia and tolerance of radiation therapy or survival outcomes.

Radiation Therapy in the Management of Primary Gastric Diffuse Large B-Cell Lymphomas: Long-Term Outcomes of 82 Patients

Our group has recently published its long-term experience treating gastric MALT lymphomas with involved site radiation therapy (ISRT) and supported the use of RT alone as standard of care for H pylori independent MALT. For primary gastric (PG) diffuse large B-cell lymphomas (DLBCL), R-CHOP is the mainstay of therapy, but RT to the stomach primarily as consolidation has rarely been analyzed. In this study, we focus on pts with PG DLBCL who received combined modality therapy. Two hundred eighty-five consecutive pts with PG lymphomas treated with RT between January 2000 and January 2021 at our institution were retrospectively identified. Baseline characteristics and follow-up data were abstracted. Overall response rate (ORR) was assessed with Lugano PET criteria and endoscopy. Overall survival (OS) was calculated using Kaplan-Meier. Toxicity was assessed with CTCAE version 4.0. Of 285 pts, 203 (71%) had PG MALT and 82 (29%) PG DLBCL. Baseline characteristics are summarized in Table 1. In the DLBCL pts, 74 (90%) received consolidation RT after limited (3-4 cycles) or full (6 cycles) chemoimmunotherapy (CT), 4 (5%) received RT after 2 lines of CT, 2 (3%) received first line RT followed by CT, 1 (1%) had 3 lines of CT and RT, and 1 (1%) was treated with surgery, 2 lines of CT, and RT. In the 74 pts who received CT+RT as first line treatment, the median RT dose was 3060 cGy (range 1620-3600). Based on post-chemo pre-RT EGD and PET, 61 (82%) pts were in CR, 7 (10%) had PR, 3 (4%) had SD and 3 (4%) pts were not assessed. Overall, 66 (89%) pts who received RT after CT achieved a CR. Of the remaining 8 (11%) pts who did not achieve a CR after RT, 4 had PR, 1 had SD, 1 was lost to FU, 1 started additional CT before response assessment and 1 pt died. The 2 pts in the DLBCL group who received first line RT achieved CR after RT. Side effects after RT were mild and limited to nausea and fatigue. The median follow-up time was 5.4 yrs (95% CI 0.4, 20.4) in DLBCL pts and 6.3 yrs (95% CI 0.3, 22.1) in MALT pts. The 5-yr OS was 80% (95% CI 71-90%) for DLBCL and 96% (95% CI 93-99%) for MALT. Adding stomach RT following chemoimmunotherapy is feasible, well-tolerated and safe. More in depth analysis PG DLBCL is underway, with a plan to compare outcomes of patients treated with CT alone versus CT followed by RT, and further analyze treatment-related toxicities, progression-free survival, and patterns of recurrence.

Treatment of Recurrent Orbital Rhabdomyosarcoma with Exenteration and HDR Brachytherapy in a Custom Mold

Rhabdomyosarcoma (RMS) is the most frequent cancer affecting the orbit in children. The orbit is classified as a favorable site for RMS as treatment with chemotherapy and radiation is effective. Local failure for patients with RMS of the orbit has ranged from 2-16% on IRS and COG protocols. In the event of local recurrence, survival is poor, and management is difficult. We report four patients with local recurrence of orbital RMS managed with orbital exenteration followed by high dose rate (HDR) brachytherapy. Four patients were treated from 2016-2022. HDR brachytherapy with Ir-192 was delivered in a custom mold of the orbit made after the orbital exenteration procedure. Brachytherapy was given in 6-7 twice daily (BID) fractions starting 1 week after the orbital exenteration. At the time of brachytherapy, patient ages were 3, 1, 7, and 7 years. Three patients had embryonal histology and underwent initial systemic therapy with ARST0331 regimen A. The fourth patient had alveolar, FOXO1 fusion positive RMS and was initially treated as per COG D9803 regimen A. All patients had received proton radiotherapy as part of initial treatment. Three received 50.40 Gy and one received 45 Gy. Patients developed biopsy-proven, recurrent disease an average of 56 weeks (range 38-77) after initial diagnosis. All patients received salvage chemotherapy before undergoing orbital exenteration at an average of 12 weeks after recurrence (range 5-16). Three patients received 30 Gy in 6 BID fractions, and one patient received 28 Gy in 7 fractions with HDR brachytherapy using an Ir-192 source. All four patients are alive without evidence of disease at an average of 27 months (range 6-70) from recurrence and 39 months (range 21-78) from initial diagnosis. All patients have acceptable orbit healing. Two patients have asymptomatic evidence of frontal lobe edema (and in one case possible necrosis) extending 1-2 cm above the orbit. This appears to be beyond the range of the brachytherapy dosimetry, but the combination of proton beam and brachytherapy are implicated. No other toxicities have occurred. Orbital RMS has a favorable prognosis, but local failure after initial combined modality therapy can be fatal. Options for successful local salvage are limited. Orbital exenteration with HDR brachytherapy in a custom mold is an effective and safe procedure for local control in these difficult cases.

Health-Related Quality of Life at Five Years for a Randomized Trial of Tri-Modality Therapy with I-125 Brachytherapy, External Beam Radiation Therapy, and Short- vs. Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer (TRIP)

To describe the patient-reported health-related quality of life (HR-QoL) outcomes at five years for a multicenter randomized trial of tri-modality therapy with iodine-125 brachytherapy, external beam radiation therapy (EBRT), and short- versus long-term androgen deprivation therapy (ADT) for high-risk localized prostate cancer (TRIP/TRIGU0907). A total of 332 men with high-risk prostate cancer were randomized to either 6 months of ADT (n = 165) or 30 months of ADT (n = 167) in conjunction with combined modality radiation therapy. For the HR-QoL assessment, general HR-QoL and disease-specific HR-QoL were measured using the Japanese version of the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite (EPIC). Patient-reported outcome questionnaires were filled out before ADT initiation, and five years after. Scores were reported as mean with the standard deviation. QoL end points were assessed as the change between pre and post treatment using paired student t-test. Changes in the International Prostate Symptom Scores (IPSS) score, including total score and subscores, were also evaluated. The study was powered according to the primary endpoint of biochemical progression free survival with HR-QoL as a secondary endpoint. In addition, recovery of testosterone level (300ng/dL or higher) was calculated as the cumulative incidence curve and compared between arms by log-rank test. The cumulative incidence of biochemical progression, and salvage ADT treatment were not different between the arms. Mean domain scores at baseline were well balanced between the two arms in all HR-QoL. There were no differences in the SF-8 assessment and the total and subscore EPIC assessments between the arms. The average sexual function score was lower in short arm versus long arm; 16.24 versus 20.24 at baseline, but not different at five years, 9.96 versus 7.78 (p = 0.164). There were no significant differences between the arms for the total and subscore IPSS. Significantly higher percentage of patients, 71.7% in the short arm recovered to a normal testosterone level at 6 years after the initiation of ADT compared to 43.2% in long arm (p<0.0001). At five years after ADT initiation, there were no significant differences in all score changes between the two arms with general HR-QoL and disease-specific HR-QoL. Most of HR-QoL returned to baseline level, and sexual function scores were low from baseline in this population. Two-years' adjuvant ADT did not affect HR-QoL at five years, although it significantly retarded testosterone recovery compared to 6 months of hormone therapy.

Developing a 4-D Dynamic Model for GammaTile Dose Distribution

GammaTile consists of Cesium-131 seeds imbedded in square 2cm tiles for intracranial resectable neoplasms. Currently, intra- and inter-tile source motion as the resection cavity evolves is not well characterized. We hypothesize that source motion is influenced by the overall tile motion which can be elucidated by 4D models of seed motion. Our patient underwent 23 fractions of EBRT after GammaTile for glioblastoma as a combined modality approach. Individual sources were identified and assigned to tiles on the post-operative, daily cone beam, and post-radiotherapy CT scans. All imaging was registered to the day 1 post-op/implant CT to utilize the same 3D space for tracking source movement. A programming environment was used to model source distances and generate dose clouds based on the seed position to create a 4D isodose volume. These dose clouds were compared to those calculated from the day 1 post-implant static isodose volume. The statistical analysis was performed using JMP®. We compared the 4D vs. static isodose volumes. The DICE score for each isodose volume was evaluated (for 30, 60, and 90 Gy the DICE scores were 0.95, 0.94, and 0.92 respectively). We found a steady decline in DICE score as the isodose line increased: DICE = -0.00065*Dose (Gy) + 0.976. Looking at the distance moved, tiles moved a mean of 5.8 mm (1.3-9.6) and appeared to remain adherent to the resection cavity wall in the first 81 days. Looking at the relative motion of the seeds within a tile, we see the tile retains a planar shape during the first 81 days and seeds move a mean of 2.2 mm (1.8-2.5) towards the center of the tile, which was a 50% contraction of the tile area. Table 1 details changes in the mean distance of source from tile center and volume occupied by all sources over time. This modeling of the tile movement/contraction is the first reported proof of concept in an approach relating tile motion with respect to sources and cavity over time. Tiles moved a mean of 5.8 mm and shrunk in the first 81 days. Discerning both how surgical cavity healing impacts seed/tile migration and how deformation impacts the dose distribution of the radiation delivered may provide a more accurate estimate of dose received by normal structures and at-risk tumor bed.

Patterns of Care for Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy between 2016-2020: An NCDB Analysis

Treatment for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease, typically requires multi-modality management consisting of radiation (RT), chemotherapy (CHT), and surgery. Despite emerging evidence that total neoadjuvant therapy (TNT) is the preferred treatment of LARC, it remains unknown what proportion of patients are receiving TNT in the United States. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a lower likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016-2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, non-adenocarcinoma histology, received RT to a non-rectum site, or received a non-definitive RT dose. Patients were determined to have received TNT if they (1) received RT and multi-agent (MA)-CHT prior to surgery, (2) had an interval of >180 days from the onset of neoadjuvant therapy to surgery if they received long course (LC)-chemoradiation (CRT) (based on 35 days for LC-CRT + 112 days for 8 cycles of MA-CHT + 30 days to surgery), or (3) had an interval of >150 days from the onset of neoadjuvant therapy to surgery if they received short course (SC)-RT (based on 5 days for SC-RT + 112 days for 8 cycles of MA-CHT + 30 days to surgery). Data were analyzed using linear regression, Chi-square test, and binary logistic regression. Of the 26,375 patients included, the median age was 60 (range 21-90) years, with the majority of patients being <65 years old (65.6%), male (62.1%), and non-Hispanic white (77.0%). A total of 5,003 (19.0%) patients received TNT, and 21,372 (81.0%) patients received classical combined modality therapy (CMT). The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016, 9.0% in 2017, 15.3% in 2018, 25.8% in 2019, to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, p = 0.040). The most common TNT regimen was MA-CHT followed by LC-CRT (73.2% of cases from 2016-2020). The proportion of patients receiving SC-RT as part of TNT significantly increased from 2.8% in 2016, 1.7% in 2017, 4.6% in 2018, 7.3% in 2019, to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, p = 0.035). On multivariate analysis, factors associated with a lower likelihood of TNT use included age >65 (OR 0.66, 95% CI 0.61-0.71, p<0.001), female gender (OR 0.92, 95% CI 0.86-0.98, p = 0.014), Black race (OR 0.87, 95% CI 0.77-0.98, p = 0.024), and T3 N0 disease (OR 0.60, 95% CI 0.52-0.70, p<0.001). TNT utilization rates have significantly increased in recent years, from 6.1% in 2016 to 34.6% in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network (NCCN) guidelines recommending TNT as the preferred approach.

Primary Small Cell Carcinoma of the Esophagus in a Large Multicenter Cohort: Prognostic Factors and Treatment Strategies in the Modern Era

Primary small cell carcinoma of esophageal (PSCCE) is a rare malignancy with aggressive behavior associated with a perceived poor prognosis. Due to its rarity, the clinical characteristics and the optimal clinical management have not yet been defined, therefore, we designed a multicenter retrospective study to analyze the prognostic factors and the impact of treatment on the prognosis of PSCCE patients. We retrospectively evaluated 704 consecutive patients with PSCCE from five participating centers between April 2008 and July 2021. The PSCCE was diagnosed based on the World Health Organization classification. Treatment strategies included surgery, radiotherapy (RT), or chemotherapy only, and combination of 2-3 treatment modalities (surgery, RT and chemotherapy). The estimated hazard rates provide the trajectory of progression and death overtime. Univariate survival analysis was conducted by using Kaplan-Meier plots, and the log-rank test was used to compare survival differences. Cox regression analysis was used to determine the independent prognostic factors in multivariate analysis. Overall, 69.0% (486/704) of the patients were male, with a median age of 63 years (range 38-96). Most of the patients were regional lymph node positive (N+, 64.0%), and nearly half with advanced stage (M+, 47.2%). With a median follow-up time of 16 months, 472 patients (67.0%) exhibited disease progression and 429 patients (60.9%) died. Following initial treatment, 85.1% (402/472) of progression/death and 80.1% (344/429) of mortalities occurred within 24 months. Consistently, the maximum annual death and progression/death hazards are highest in the 15.6 months and 9.6 months. The overall survival (OS) rates at 1, 3 and 5 years for all patients were 65.1%, 26.5% and 18.3%, respectively. Univariate survival analysis showed that ECOG score, alcohol abuse, TNM stage, N stage, and M stage were correlated with OS (P <0.05). Multivariate analysis showed that the N stage (HR: 1.378, P = 0.018) and M stage (HR: 1.945, P <0.001) carried independent prognostic factors for OS. In the term of treatment, the OS rates for M- patients treated with combined modality therapy (CMT, surgery±radiotherapy/chemotherapy) were better than those treated with surgery alone or radiotherapy/chemotherapy (3-year OS: 36.7% VS 25.6% VS 32.2%; P = 0.045). The OS rates for M+ patients treated with chemotherapy alone, radiotherapy alone, or radiotherapy combined with chemotherapy were no significant differences (3-year OS: 12.2% VS 19.4% VS 11.1%; P = 0.400). PSCCE is characterized by a high degree of malignancy with high risks of lymphatic and distant metastasis, N and M stages are the most important prognostic factor. In terms of treatment, comprehensive treatment is most likely to benefit patients without distant metastasis.

Radiotherapy dose de-escalation in patients with high grade non-Hodgkin lymphoma in a real-world clinical practice.

The standard treatment of non-Hodgkin lymphoma (NHL) comprises combined modality treatment, radiotherapy (RT), and chemotherapy with rituximab which has significantly improved both disease-free survival (DFS) and overall survival (OS). However, there is no uniformity in radiation dose usage in these patients. In this retrospective study, we compared lower radiation dose with higher in patients with aggressive NHL. From 2007 to 2017, treatment records of all high-grade NHL or diffuse large B-cell lymphoma and non-central nervous system NHL were included. We compared response rates, OS and DFS of patients who received ≤30 Gy RT to those with >30 Gy. Univariate and multivariate analyses were done to determine factors affecting prognosis, i.e., age, sex, stage, International Prognostic Index (IPI), adding rituximab, and radiation dose. A total of 184 NHL patients treated with combined modality or radiation alone having complete follow-up details were analyzed. At median follow-up of 66.8 months, 5-year OS was 72.8% in high-dose group versus 69.9% in low-dose group (p = 0.772) and 5-year DFS 64.7% versus 64.1% (p = 0.871). Patients having early-stage disease receiving low dose and those with advanced disease treated with >30 Gy had better OS and DFS though not statistically significant. Adding rituximab was associated with significantly better OS and DFS irrespective of radiation dose delivered. High IPI score and omitting rituximab were the only factors that significantly worsened both OS and DFS. Acute radiation toxicities were comparable in both groups (p = 0.82). Among late toxicities, no patient developed a second malignancy and 5% died due to cardiovascular complications (p = 0.595) though only two patients (1.1%) had received thoracic radiation. The two groups had comparable response rates, acute toxicities, DFS and OS. This study suggests that RT dose reduction may be possible in high-grade NHL without compromising the DFS and OS.

The SP/NK1R system promotes the proliferation of breast cancer cells through NF-κB-mediated inflammatory responses.

Numerous molecules have been introduced to participate in the formation of breast cancer, the most common malignancy in women. Among them, neuropeptide substance P (SP) and its related receptor neurokinin-1 receptor (NK1R) have attracted unprecedented attention in tumorigenesis processes. In this study, we investigated the effect of the SP/NK1R pathway on the induction of oxidative stress in breast cancer and examine the therapeutic potential of NK1R inhibition in this malignancy. MCF-7 cells were treated with varying concentrations of SP and aprepitant, an FDA-approved NK1R antagonist, either as a single drug or in a combined modality. Resazurin assay was used to evaluate the anti-cancer ability of aprepitant. The alteration in the intracellular levels of reactive oxygen species (ROS) and gene expression were determined using ROS assay and the qRT-PCR analysis, respectively. The stimulation of the SP/NK1R axis in the MCF-7 cells was coupled with the accumulation of ROS as well as upregulation of NF-κB and its related pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and IL-6. In contrast, the suppression of NK1R by aprepitant halted the viability of MCF-7 cells, at least partly due to p53-mediated upregulation of p21. Moreover, aprepitant attenuated the oncogenic properties of SP by preventing the oxidative property of this neuropeptide. Overall, our results suggest that the SP/NK1R pathway might play a critical role in breast cancer pathogenesis, probably through inducing ROS/NF-κB-mediated inflammatory responses. Moreover, it seems that blockage of the axis has promising therapeutic value against breast cancer cells. Schematic representation proposed for the plausible mechanism by which the stimulation of the SP/NK1R might induce oxidative stress in breast cancer-derived MCF-7 cells. Once SP interacts with NK1R, this signaling axis could disturb the balance between the expression of p53 and NF-κB, an event that leads to the accumulation of ROS within MCF-7 cells. The produced ROS, in turn, elevates the expression of pro-inflammatory cytokines (TNF-α and IL-6) and downregulates the expression of p21. On the other hand, aprepitant, an antagonist of NK1R, could reduce the survival of proliferative capacity of MCF-7 cells by decreasing the intracellular levels of ROS and p53-mediated up-regulation of p21. Along with the effect on p53, aprepitant could also reduce the expression of NF-κB and its related pro-inflammatory cytokines.

Autoencoder-based multimodal prediction of non-small cell lung cancer survival

The ability to accurately predict non-small cell lung cancer (NSCLC) patient survival is crucial for informing physician decision-making, and the increasing availability of multi-omics data offers the promise of enhancing prognosis predictions. We present a multimodal integration approach that leverages microRNA, mRNA, DNA methylation, long non-coding RNA (lncRNA) and clinical data to predict NSCLC survival and identify patient subtypes, utilizing denoising autoencoders for data compression and integration. Survival performance for patients with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) was compared across modality combinations and data integration methods. Using The Cancer Genome Atlas data, our results demonstrate that survival prediction models combining multiple modalities outperform single modality models. The highest performance was achieved with a combination of only two modalities, lncRNA and clinical, at concordance indices (C-indices) of 0.69 ± 0.03 for LUAD and 0.62 ± 0.03 for LUSC. Models utilizing all five modalities achieved mean C-indices of 0.67 ± 0.04 and 0.63 ± 0.02 for LUAD and LUSC, respectively, while the best individual modality performance reached C-indices of 0.64 ± 0.03 for LUAD and 0.59 ± 0.03 for LUSC. Analysis of biological differences revealed two distinct survival subtypes with over 900 differentially expressed transcripts.

Evaluation and management of enuresis in the general paediatric setting.

Assessing enuresis involves distinguishing monosymptomatic from non-monosymptomatic for this common paediatric problem, and identifying concomitant comorbidities. Addressing co-occurring factors concurrently ensures the best opportunity for a satisfactory outcome. Treatment begins with patient and family education on the natural history of enuresis and practical behavioural guidance. Evidence to support particular interventions is limited, and children and families should be involved when choosing appropriate therapy. Enuresis alarms and desmopressin are treatment options when more active intervention is desired. Clinical refinements and combined treatment modalities are emerging.

SURVIVAL OUTCOMES AMONG PATIENTS WITH HIGH-GRADE GLIOMA: A SINGLE INSTITUTION RETROSPECTIVE STUDY

BackgroundThe prognosis for glioma patients is poor, despite recent advances in diagnosis and treatment. Understanding Glioma’s clinical characteristics and predictive factors is crucial for patient treatment and management.&#x0D; ObjectivesTo assess the survival duration of HGG patients at a single facility and to discover clinical determinants of treatment outcome in HGG treated with a combined modality approach in Zhianawa Cancer Center.&#x0D; Patients and MethodsThis study included 133 patients with high-grade gliomas diagnosed between January 2015 and January 2020; these patients were referred to the Zhianawa Cancer Center. A retrospective analysis of the clinical data included survival outcomes, tumour characteristics, and demographic information. While the Cox regression model was used for the evaluation of multivariate data to look at the risk factors for mortality, on the other hand, survival data were analyzed using Kaplan-Meier curves with a log-rank test.&#x0D; ResultsIn this particular patient cohort, grade IV glioma (83.9%), grade III glioma (16.1), and glioblastoma (81.4%) were the most common pathological types. A poor prognosis was associated with not using temozolomide, having a Karnofsky Performance Score (KPS) of less than 70%, and not receiving radiotherapy. Univariate analysis showed low KPS (70) to increase the risk of mortality. Patients who had radiotherapy with normal fractionation, concurrent chemotherapy, and radiotherapy adjuvant chemotherapy had the highest overall survival rates.&#x0D; ConclusionMortality was significantly related to aging, absence of seizures, presence of motor alteration, pathological grade IV gliosarcoma, glioblastoma multiform, and non-standard radiation dose.

A Generic, Multimodal Geospatial Data Alignment System for Aerial Navigation

We present a template matching algorithm based on local descriptors for aligning two geospatial products of different modalities with a large area asymmetry. Our system is generic with regards to the modalities of the geospatial products and is applicable to the self-localization of aerial devices such as drones and missiles. This algorithm consists in finding a superposition such that the average dissimilarity of the superposed points is minimal. The dissimilarity of two points belonging to two different geospatial products is the distance between their respective local descriptors. These local descriptors are learned. We performed experiments consisting in estimating a translation between optical (Pléiades) and SAR (Miranda) images onto vector data (OpenStreetMap), onto optical images (DOP) and onto SAR images (KOMPSAT-5). Each remote sensing image to be aligned covered 0.64 km2, and each reference geospatial product spanned over 225 km2. We conducted a total of 381 alignment experiments, with six unique modality combinations. In aggregate, the precision reached was finer than 10 m with 72% probability and finer than 20 m with 96% probability. This is considerably more than with traditional methods such as normalized cross-correlation and mutual information.

Outcome and prognostic factors of pediatric patients with Hodgkin lymphoma: a single-center experience

BackgroundHodgkin lymphoma (HL) is a highly curable malignant tumor. Risk-adapted treatment for children with HL aims to maximize survival while minimizing toxicity. The purpose of this study is to evaluate the outcome and prognostic characteristics of Egyptian pediatric HL patients treated at the National Cancer Institute (NCI), Cairo University.MethodsAll newly diagnosed cases of classic HL treated between January 2016 and December 2018 were included in this study.ResultsThe median age at initial presentation was 8 years in 69 eligible individuals, with a male-to-female ratio of 4.7:1. Eighteen percent of patients had an elevated erythrocyte sedimentation rate (ESR) of more than 50, 42% had more than three lymph node (LN) group involvements, 18.8% had bulky disease, 52.2% were at an advanced stage, and 34% had B symptoms. Age > 15 years, B symptoms, > 3 LN group involvement, extra-nodal disease, and advanced stages significantly affected the overall survival rate (OS) (P-values = 0.03, 0.033, 0.008, 0.017, and 0.032). There was no statistically significant difference between patients who got combined modality therapy (CMT) and those who received chemotherapy alone (3-year OS and event-free survival (EFS) were 95.5% and 87.6% vs. 89.9% and 83.3%, P-values of 0.70 and 0.90). Patients with an interim-negative positron emission tomography-computed tomography (PET-CT) had a 3-year OS of 94.7%, compared to 74.1% in patients with an interim-positive PET-CT (P = 0.06), suggesting that rapid early response (RER) is a significant prognostic factor. There was no statistically significant survival difference between patients with a negative interim PET-CT who got CMT and those who received chemotherapy alone (3-year OS and EFS: 100% and 88.2% vs. 95% and 90%; P = 0.35 and 0.70, respectively). Three-year OS was 93.3% and 100%, and EFS was 74.3% and 100% (P = 0.495 and 0.196%) for those who got 15 Gy versus those who received 20 Gy or more, respectively. At the end of the study, the OS and EFS at 3 years for the whole group were 91.9% and 83.6%.ConclusionTreatment with risk- and response-adaptive treatment should be the standard of care for treating pediatric patients with HL.

A case report of long-term successful use of maintenance therapy with PARP inhibitors in the primary treatment of advanced brca-associated ovarian cancer

Background. Ovarian cancer is the third most common cancer of the female reproductive system after cervical and uterine cancer and is diagnosed at stage III–IV in 2 out of 3 cases. Maintenance therapy with PARP inhibitors signifcantly prolongs disease-free and overall survival. The purpose of the study was to demonstrate long-term remission in a patient with advanced ovarian cancer using maintenance therapy with PARP inhibitors (olaparib). Description of the clinical case. A 54-year-old female patient with verifed stage IV ovarian cancer, peritoneal carcinomatosis and left-sided pleurisy received combined modality treatment, including 2 courses of neoadjuvant chemotherapy with paclitaxel/carboplatin, cytoreductive surgery and 6 courses of postoperative chemotherapy with docetaxel/cisplatin. The patient was diagnosed with a somatic BRCA2 gene mutation (c.3708delA), which was detected by tumor DNA sequencing. The patient received maintenance therapy with olaparib for 38 months, resulting in no evidence of disease progression. Conclusion. This clinical case demonstrates the feasibility of using maintenance therapy with PARP inhibitors in a patient with initially disseminated platinum-sensitive ovarian cancer. Olaparib maintenance therapy provides stable long-term remission with no signs of adverse events and determined effect on quality of life of the patient.

Development and external validation of the multichannel deep learning model based on unenhanced CT for differentiating fat-poor angiomyolipoma from renal cell carcinoma: a two-center retrospective study.

There are undetectable levels of fat in fat-poor angiomyolipoma. Thus, it is often misdiagnosed as renal cell carcinoma. We aimed to develop and evaluate a multichannel deep learning model for differentiating fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma (RCC). This two-center retrospective study included 320 patients from the First Affiliated Hospital of Sun Yat-Sen University (FAHSYSU) and 132 patients from the Sun Yat-Sen University Cancer Center (SYSUCC). Data from patients at FAHSYSU were divided into a development dataset (n = 267) and a hold-out dataset (n = 53). The development dataset was used to obtain the optimal combination of CT modality and input channel. The hold-out dataset and SYSUCC dataset were used for independent internal and external validation, respectively. In the development phase, models trained on unenhanced CT images performed significantly better than those trained on enhanced CT images based on the fivefold cross-validation. The best patient-level performance, with an average area under the receiver operating characteristic curve (AUC) of 0.951 ± 0.026 (mean ± SD), was achieved using the "unenhanced CT and 7-channel" model, which was finally selected as the optimal model. In the independent internal and external validation, AUCs of 0.966 (95% CI 0.919-1.000) and 0.898 (95% CI 0.824-0.972), respectively, were obtained using the optimal model. In addition, the performance of this model was better on large tumors (≥ 40mm) in both internal and external validation. The promising results suggest that our multichannel deep learning classifier based on unenhanced whole-tumor CT images is a highly useful tool for differentiating fp-AML from RCC.

Differentiated approach to adjuvant neutron therapy in patients with locally advanced breast cancer, taking into account signifcant prognostic factors

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods. The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results. A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ2 =43.7; p&lt;0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found. Conclusion. Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype.