Trimodality Therapy Research Articles

Risk stratification of postoperative cardiopulmonary toxicity after trimodality therapy for esophageal cancer.

Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes. Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin etal. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used. From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and proton therapy (19%). 61 patients had major CPTTB (score ≥ 70). Increasing CPTTB was predictive of decreased OS (p<0.001), lengthier post-esophagectomy length of stay (LOS, p<0.001), and death or readmission within 60 days of surgery (DR60, p<0.001). Major CPTTB was also predictive of decreased OS (hazard ratio = 1.70, 95% confidence interval: 1.17-2.47, p=0.005). The RPA-based risk score included: age ≥ 65, grade ≥ 2 nausea or esophagitis attributed to chemoradiation, and grade ≥ 3 hematologic toxicity attributed to chemoradiation. Patients treated with 3D radiotherapy had inferior OS (p=0.010) and increased major CPTTB (18.5% vs. 6.1%, p<0.001). CPTTB predicts for OS, LOS, and DR60. Patients with 3D radiotherapy or age ≥ 65 years and chemoradiation toxicity are at highest risk for major CPTTB, predicting for higher short and long-term morbidity and mortality. Strategies to optimize medical management and reduce toxicity from chemoradiation should be strongly considered.

Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT).

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4-94.9) and 49.5% (95% CI:26.5-68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging.

Trimodality therapy with carboplatin/paclitaxel (CP) or FOLFOX (FFX) for esophageal/esogastric junctional cancer (EC/EGJ): Expanded safety and efficacy data from PROTECT.

370 Background: When combined to preoperative radiation therapy (RT), CP and FFX regimen provide both high complete resection (R0) rate for EC/EGJ cancer (Adenis, ASCO 2022). However, it appeared that neoadjuvant chemoradiation (nCRT) with CP is associated with a severe postoperative morbidity rate higher than expected. We present here the expanded safety and efficacy analyses from the PROTECT trial. Methods: PROTECT is a randomized, phase 2 trial which included stage II/III and ECOG PS ≤2 EC or Siewert I-II EGJ cancers. Patients (pts) received FFX or CP with concurrent RT (41.4Gy, 1.8Gy, 23 fractions), followed by surgery 4-8 weeks after completion of nCRT (Messager, BMC Cancer 2016). Co-primary endpoints were proportion of R0 rate and proportion of Clavien-Dindo severe postoperative morbidity. Main secondary endpoints were nCRT and postoperative safety (NCI CTCAE v.4), DFS and OS. Results: 41/50 (82%) and 39/50 (78 %) pts received the planned chemo cycles and concurrent RT in FFX and CP arms, respectively. Grade (gr.) 3–4 AEs related to nCRT (FFX 14/50, 28%; CP 14/50, 28%) occurring in ≥5% of pts included lymphopenia (n=3, 6%; n=4, 8%), neutropenia (n=1, 2%; n=3, 6%), fatigue (n=2, 4%; n=0) and esophagitis-related to RT (n=1, 2%; n=1, 2%). No death was reported during nCRT. Surgery (FFX and CP; mini invasive: 15 and 15, hybrid: 22 and 21, open: 7 and 12) was performed in 44 and 48 pts, in FFX and CP groups, respectively. The main gr. III-V surgical complications (Clavien-Dindo scale) occurring in ≥5% of pts included esophageal fistula (n=2/43 evaluable pts, 6%; 8/48, 17%), conduit necrosis (n=2, 5%; n=1, 2%), ARDS (n=3, 7%; n=3, 6%), pleural effusion (n=3, 7%; n=4, 8%), and haemorrhage (n=0; n=3, 6%). There were no postoperative deaths. With a median follow-up of 54m, median DFS were 12.3m and 20m (HR=0.84; 95%CI: 0.52-1.35; p=0.48) and median OS were 31.7m and 45.8m (HR=0.79; 95%CI: 0.47-1.32; p=0.36) in FFX and CP arms, respectively. Prognostic factors significantly associated to DFS in univariate analysis were: R0 resection, TRG1-2 and ypT0N0 status. Conclusions: A higher than expected number of severe esophageal fistula was observed in the CP arm. We could not demonstrate a significant benefit of CP compared to FFX in terms of survival outcomes, but the study was not primarily designed to specifically address this issue. Clinical trial information: NCT02359968 .

Phase 1b study to assess the safety of neoadjuvant trifluridine/tipiracil with concurrent radiation in resectable stage II/III rectal cancer.

TPS274 Background: Treatment of locally advanced rectal cancer currently involves tri-modal therapy with pre-operative chemo-radiation (CRT), surgery, and combination chemotherapy. Total neoadjuvant therapy (TNT) is emerging as an important treatment pathway that can increase rates of complete response (CR) leading to better overall outcomes. Novel radio-sensitizing agents may improve rates of CR. Trifluridine/tipiracil (TFD/TPI) is a novel fluoropyrimidine that has demonstrated clinical efficacy in patients with treatment-refractory metastatic colorectal cancer. Importantly, TFD/TPI has superior radio-sensitization in vitro compared to 5-fluorouracil, and we hypothesize that this can improve the tumor response of patients. This phase 1 study assesses the safety and preliminary efficacy of using TFD/TPI for long-course CRT for rectal cancer followed by FOLFOX chemotherapy in the TNT setting. Methods: NCT04104139 is a prospective, dose-finding phase I study using Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) of TFD/TPI with concurrent standard dose/fractionation radiation for resectable rectal cancer. Adults with previously untreated rectal adenocarcinoma, with clinical stage II (T3-4aN0) and stage III (T1-4aN1+) by MRI and endoscopy are eligible. Patients must first receive CRT with standard radiation (45-50 Gy over 25-28 fractions) followed by up to 8 cycles of standard FOLFOX, or alternatively 5 cycles of CAPOX chemotherapy. During CRT, the first dose level of TFD/TPI is PO 25mg/m2 twice a day from Mon to Fri (5 weekdays) alternating on weeks 1, 3, and 5 concurrent with 5-6 weeks of radiation. The second dose level is 30mg/m2, and third dose level is 35mg/m2. The MTD of TFD/TPI in combination with radiation is the dose corresponding to a dose limiting toxicity (DLT) probability of 30% using the BOIN design with escalation/de-escalation of each dose level occurring in cohorts of 3 participants until a maximum total of 18 participants, sub-total of 12 patients within one dose level, or another stopping rule based on serious toxicities. The primary endpoint is proportion of DLTs for TFD/TPI at MTD. Secondary endpoints include overall tolerability profile, delayed toxicities during FOLFOX, rates of clinical CR, rates of pathologic CR, and correlative biomarkers. The study was activated December 2019 and has accrued 8 of intended 18 patients. Clinical trial information: NCT04104139 .

Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Chemoradiotherapy Versus Chemoradiotherapy Alone in Muscle-invasive Bladder Cancer: The MK-3475-992/KEYNOTE-992 Trial

Trimodal therapy comprising maximal transurethral resection of bladder tumor followed by radiation therapy with sensitizing chemotherapy is an alternative treatment option for muscle-invasive bladder cancer. This approach has shown comparable results to those with neoadjuvant chemotherapy followed by radical cystectomy in retrospective analyses for selected patients. Efforts to improve oncological outcomes of bladder-preserving strategies have converged on adding perioperative immunotherapy as a fourth treatment modality to the current trimodal design.

Inverse probability treatment weighting comparison of radical cystectomy to trimodality therapy for cT2-cT4 muscle invasive bladder cancer

Inverse probability treatment weighting comparison of radical cystectomy to trimodality therapy for cT2-cT4 muscle invasive bladder cancer

The Effect of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients With Stage III Non-Small Cell Lung Cancer

Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. Thirty-two percent of patients resided in an FPA (n=183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P=.001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P=.002), lower pre-CRT body mass index (BMI) (P=.026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P=.005) or after CRT (15.1 vs 28.1 months, P=.002), residing in an FPA resulted in an OS detriment. We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

Skeletal muscle area predicts the outcomes of non-small-cell lung cancer after trimodality therapy.

Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions.

Programmed-stimuli responsive carrier-free multidrug delivery system for highly efficient trimodal combination therapy

Programmed response, carrier-free, and multimodal therapy drug delivery systems (DDS) are promising solutions to multidirectional cytotoxic effects, inefficient antitumor, and severe side effects for cancer therapy. Here, three widely used clinical drugs, interferon α1b (IFNα1b), indocyanine green (ICG), and doxorubicin (DOX), were prepared into carrier-free DDS IFNα1b-ICG-DOX (IID) by a simple one-step method without additional any reagents. IID can achieve smart and programmed DDS by combining low pH and near-infrared (NIR) light stimuli-responsive controlled release. In pH = 7.4 environments, our IID is about 380 nm in size with negative charge rounded particles; while they enter into the acid environment (pH < 7), hydrogen ions (H+) trigger DOX release, their size becomes larger and the surface charge turns positive. These larger particles are rapidly disintegrated after exposure to NIR light and then the remaining DOX, IFNα1b, and ICG are released. In vivo, the IID with larger size and positive charge resulting from low pH is is easy to accumulate in tumor tissue. Tumors can be exposed to NIR light when needed to control the release of these three drugs. Hence, DOX, ICG, and IFNα1b can be enriched in the tumor to the high efficiency of combined chemotherapy, photothermal therapy, and immunotherapy.

Health-related quality of life after curative treatment for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which the gold-standard treatment is radical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy. Bladder-sparing strategies such as trimodal therapy (TMT) have also emerged to improve health-related quality of life (HRQoL) of patients. However, an improved understanding of the effect of all these treatment modalities on HRQoL is essential to provide personalized patient care. Different combinations of generic, cancer-specific and bladder cancer-specific questionnaires can be used as instruments for HRQoL evaluation in patients with MIBC before and after curative treatments, which can largely affect multiple domains of HRQoL including general health as well as physical, functional, social and emotional well-being. However, diagnosis of MIBC per se is also likely to affect HRQoL, and the perspective of cure after RC or TMT could induce a return to baseline HRQoL values for most of these domains. A considerable amount of data on HRQoL after RC is available, but conflicting results have been reported regarding the effect of urinary diversion (ileal conduit or orthotopic neobladder) and surgical approach (open or robotic surgery) on patient quality of life. Data on HRQoL after TMT are scarce, and additional comparative studies including patients receiving RC (especially using ileal orthotopic neobladder) are needed.

Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort.

To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. The median OS was 71.4 months (interquartile range: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89-0.98); 0.94 (0.89-0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09-0.53); 0.30 (0.12-0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01-1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08-6.57)] and adventitial involvement [2.54 (1.36-4.72)] also influenced OS, while involved margins [3.12 (1.24-7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44-0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57-0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.

Malignant mesothelioma among US Medicare beneficiaries: incidence, prevalence and therapy, 2016–2019

ObjectivesMesothelioma is a rare, aggressive cancer caused by exposure to asbestos fibres. Mesothelioma patients who receive trimodal therapy (chemotherapy, surgical resection and radiation) survive longer than those who receive two...

New molecular and immunologic targets of therapy for esophageal cancer and the prospects for ongoing and future clinical trials.

Esophageal cancer is a deadly disease worldwide. Advancements in diagnosis, surgical technique, chemotherapy, and radiotherapy have improved survival over the years. While targeted therapy and immunotherapy have significantly impacted survival for patients with advanced disease, they have also been demonstrating efficacy when added to trimodality therapy for locoregional disease. This review focuses on molecular and immunologic targets of therapy for esophageal cancer and the prospects for ongoing and future clinical trials.

Prognostic significance of tumor regression grade in esophageal squamous cell carcinoma after neoadjuvant chemoradiation.

Trimodal therapy (neoadjuvant chemoradiotherapy followed by esophagectomy) for locally advanced esophageal squamous cell carcinoma (ESCC) is associated with a significant survival benefit. Modified Ryan score is an effective tool to evaluated the tumor regression grade (TRG) after neoadjuvant therapy. The aim of this study was to evaluate the prognostic value of TRG for overall survival (OS) and disease-free survival (DFS) in ESCC patients undergoing neoadjuvant chemoradiation. The study retrospectively reviewed 523 ESCC patients who underwent neoadjuvant chemoradiotherapy and radical esophagectomy at Jinling Hospital from January 2014 to July 2020. Kaplan-Meier curves with log-rank test and Cox regression model were used to evaluate the prognostic factor of TRG based on modified Ryan scoring system on OS and DFS. After application of inclusion and exclusion criteria, 494 patients with ESCC following neoadjuvant chemoradiotherapy and radical esophagectomy were available for analysis. The TRG scores are significantly associated with smoke history (p = 0.02), lymphovascular invasion (LVI) and/or peripheral nerve invasion (PNI) (p < 0.01), and postoperative adjuvant therapy (p < 0.01). Meanwhile, tumor characteristics including tumor length (p < 0.01) and tumor differentiation grade (p < 0.01) are also significantly associated with TRG score. The results of multivariable Cox regression modal showed that TRG is not an independently prognostic factor for OS (p = 0.922) or DFS (p = 0.526) but tumor length is an independently prognostic factor for DFS (p = 0.046). This study evaluated the prognostic value of modified Ryan scoring system for ESCC after trimodal therapy and concluded that modified Ryan scoring system can predict survival and recurrence rates but is not an independently prognostic factor for OS and DFS.

Understanding Financial Toxicity in Patients with Head and Neck Cancer: A Systematic Review.

Cancer treatment often results in financial burdens for patients including healthcare costs as well as treatment-induced disability leading to "financial toxicity" (FT) and decreased quality of life. The purpose of this review is to describe FT related to head and neck cancer (HNC) treatment, including quantifications of direct and indirect costs and descriptions of measurement tools. PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify articles published before April 2022. Full-text published studies were included if they assessed direct or indirect costs of HNC treatment; studies were excluded if they did not focus on HNC or financial burden. The risk of bias was assessed, and the results of the studies were synthesized. Database searches yielded 530 unique studies, and 33 studies met the criteria for inclusion. Medical expenses for patients with HNC were higher than for patients with other cancers or controls in several studies. Major surgical procedures, neck dissection, free-flap reconstruction, and intensive care unit admission increased hospital costs. Trimodal therapy with surgery plus chemoradiation represented the most expensive treatment, and chemoradiation increased complication-related health care costs. In several studies, >50% of patients treated for HNC were disabled and did not return to work. One of the greatest contributors to the indirect cost of HNC treatment is the loss of lifetime wages. Patients with HNC are at risk for depression, anxiety, and social isolation, which are linked to a decreased quality of life and treatment non-adherence. The only tools used to assess FT in patients with HNC are the Comprehensive Score for financial Toxicity (COST) and the Financial Index of Toxicity (FIT). Financial toxicity is highly prevalent among patients with HNC. Further research is needed to validate the assessment tools for quantifying FT in HNC patients.

Designed synthesis of prussian blue@Cu-doped zinc phosphate nanocomposites for chemo/chemodynamic/photothermal combined cancer therapy.

Designing a multifunctional nanoplatform that combines multiple treatments has emerged as an innovative cancer treatment strategy. A simple and clear route is put forward to develop Cu2+-doped zinc phosphate coated prussian blue nanoparticles (designated as PB@Cu2+/ZnP NPs) integrating tri-modal therapy (chemo, chemodynamic and photothermal therapy) for maximizing anti-tumor efficacy. The obtained PB@Cu2+/ZnP NPs possess drug loading capacity due to the mesoporous structure present in the Cu2+-doped ZnP shell. In addition, the Cu2+-doped ZnP shell can gradually degrade in response to the mildly acidic tumor microenvironment to release DOX and Cu2+, where the released drug plays the role of chemotherapy agent and the Cu2+ can react with intracellular glutathione to achieve a Cu-mediated Fenton-like reaction for chemodynamic therapy. Moreover, under laser irradiation, the heat garnered by the photothermal conversion of PB can be applied for photothermal therapy and enhance the generation of toxic ˙OH as well as the amount of DOX released, further boosting chemo- and chemodynamic therapy to realize a combined therapy. Importantly, the PB@Cu2+/ZnP NPs effectively limit the growth of tumors via the coordinated action of chemo/chemodynamic/photothermal therapy and no noticeable systematic toxicity can be found in mice. Taken together, the PB@Cu2+/ZnP NPs can act as a prospective therapeutic nanoplatform for multi-modal therapy of tumors.

Trimodality therapy of malignant pleural mesothelioma with helical tomotherapy.

The purpose of this study was to determine the efficacy and tolerability of hemithoracic radiotherapy implemented with helical tomotherapy (HTT) in malignant pleural mesothelioma (MPM) patients. Between October 2018 and December 2020, data from 11 MPM patients who received trimodality therapy, including lung-sparing surgery (pleurectomy-decortication, P/D), adjuvant chemotherapy (cisplatin+ pemetrexed), and radiotherapy, were retrospectively reviewed. HTT was used to deliver a total of 30 Gy, 50-54 Gy or 59.4-60 Gy to R2 disease with 1.8-2 Gy daily doses. Descriptive data are presented in number (percentage) or median (minimum- maximum). The Kaplan-Meier method was used to calculate survival data. In patients with toxicities, the risk organ doses were compared using the Mann-Whitney U test. The median follow-up was 20.5 (12-30) months. Two-year local control, disease-free, and overall survival rates were 48.5%, 49%, and 77.9%, respectively. The median prescribed dose for planning target volume (PTV) was 50.4±8.7 (30-60) Gy. Mean dose (Dmean) of total lung was 19.9±6 (10.4-26) Gy; the V20 (%) of ipsilateral and contralateral lungs were 89.±11.2 (62.7-100) and 0.7±2.1 (0.49-5.9), respectively. Esophageal Dmean and maximum doses (Dmax) were found as 21.7±8.4 (7.4-34) and 53.1±10.4 (25.4-64.4) Gy, respectively. V30 (%) and Dmean of heart were 22.3%±13.4% (3.9-47) and 21±5.7 (10.8-29.3) Gy, respectively. Dmax of medulla spinalis (MS) was 38.6± 1.3 (13.7-48) Gy. Grade 1-2 radiation pneumonitis (RP) developed in 4 (36.4%) and esophagitis in 2 (18.2%) patients. RP was found to be associated with MS and esophageal doses (p<0.05). Myelitis was diagnosed in 1 (9.1%) patient (MS Dmax: 29 Gy). HTT can be used as part of trimodality therapy for MPM patients with acceptable toxicities. MS and esophageal doses should be considered for radiation pneumonitis risk, and new dose constraints for these organs should be defined.

An overview of inflammatory breast cancer

Inflammatory breast cancer is an uncommon and severe malignancy that frequently goes undiagnosed at first because it presents similarly to more benign breast diseases like mastitis, resulting in delayed treatment. Inflammatory breast cancer affects 1% to 5% of all occurrences of breast cancer and accounts for 8% to 10% of all breast cancer-related deaths. Erythema, skin abnormalities, nipple inversion, edema, and warmth of the affected breast are all signs of inflammatory breast cancer. Recognized risk factors for inflammatory breast cancer include young age at the time of diagnosis, obesity and African American ethnicity. Rapid onset within 3 months and pathologic evidence of invasive carcinoma leads to diagnosis of disease further including erythema occupying at least one-third of the breast, tumour may or may not be present in this case. Chemotherapy, surgery, and radiation make up the trimodal therapy used to treat inflammatory breast cancer. A modified radical mastectomy performed as part of an aggressive surgical strategy improves survival rates. Although patients with inflammatory breast cancer have worse outcomes than those with noninflammatory breast cancer, those who complete trimodal therapy have a positive locoregional control rate, highlighting the significance of an early diagnosis. Physicians must be aware and examine any clinical manifestation of inflammatory breast cancer if present to make a prompt diagnosis and refer patient for expert care timely also awareness and cancer screening can help in prevention of disease. The purpose of this research is to review the available information about an overview of inflammatory breast cancer.

The Role of Age and Comorbidities in Esophagogastric Cancer Chemoradiation of the Frail Elderly (>70 Years): An Analysis from a Tertiary High Volume-Center

Elderly patients > 70 years of age with esophageal cancer (EC) represent a challenging group as frailty and comorbidities need to be considered. The aim of this retrospective study was to evaluate the efficacy and side effects of curative chemoradiation therapy (CRT) with regard to basic geriatric screening in elderly patients in order to elucidate prognostic factors. Thirty-four elderly patients > 70 years with EC treated at our cancer center between May 2014 and October 2018 fulfilled the selection criteria for this retrospective analysis. Treatment consisted of intravenous infusion of carboplatin/paclitaxel or fluorouracil (5-FU)/cisplatin with the intention of neoadjuvant or definite chemoradiation. Clinicopathological data including performance status (ECOG), (age-adjusted) Charlson comorbidity index (CCI), Frailty-scale by Fried, Mini Nutritional Assessment Short Form, body mass index, C-reactive protein to albumin ratio, and treatment-related toxicity (CTCAE) were assessed. Data were analyzed as predictors of overall survival (OS) and progression-free survival (PFS). All patients (ten female, 24 male) received combined CRT (22 patients in neoadjuvant, 12 patients in definite intent). Median age was 75 years and the ECOG index between 0 and 1 (52.9% vs. 35.3%); four patients were rated as ECOG 3 (11.8%). Median follow-up was 24 months. Tumors were mainly located in the lower esophagus or esophagogastric-junction with an T3 stage (n = 25; 75.8%) and N1 stage (n = 28; 90.3%). 15 patients (44.1%) had SCC, 19 patients (55.9%) AC. 26 of the patients (76.5%) were scored as prefrail and 50% were in risk for malnutrition (n = 17). In relation to the BMI, ten patients (29.4%) were ranked as overweight, and 15 patients were presented in a healthy state of weight (44.1%). Grade 3 acute toxicity (or higher) occured in nine cases (26.5%). Most of the patients did not show any late toxicities (66.7%). Trimodal therapy provides a significant prolonged OS (p = 0.049) regardless of age, but without impact on PFS. Our analysis suggests that chemoradiation therapy is feasible for elderly patients (>70 years) with tolerable toxicity. Trimodal therapy of EC shows a positive effect on OS and PFS. Further studies are needed to elucidate benefitting subgroups within the elderly. In addition to age, treatment decisions should be based on performance status, nutritional condition and multidisciplinary validated geriatric screening tools.

Differences in Cancer-Specific Mortality after Trimodal Therapy for T2N0M0 Bladder Cancer according to Histological Subtype.

We aimed at assessing the impact of non-urothelial variant histology (VH), relative to urothelial carcinoma of the urinary bladder (UCUB), on cancer-specific mortality (CSM) in T2N0M0 bladder cancer patients treated with trimodal therapy (TMT). TMT patients treated for T2N0M0 bladder cancer were identified within the Surveillance, Epidemiology, and End Results database (2000−2018). Patients who underwent TMT received trans-urethral resection of the bladder tumor, chemotherapy, and radiotherapy. CSM-FS rates were tested using Kaplan−Meier plots and multivariable Cox-regression (MCR) models according to histological subtype: UCUB vs. neuroendocrine carcinoma vs. squamous cell carcinoma vs. adenocarcinoma. A total of 3846 T2N0MO bladder cancer patients treated with TMT were identified. Of these, 3627 (94.3%) harbored UCUB, while 105 (2.7%), 85 (2.2%), and 29 (0.8%) harbored neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma, respectively. In Kaplan−Meier analyses, 3-yr CSM-FS rates were 57% for UCUB, 51% for neuroendocrine carcinoma, 35% for squamous cell carcinoma, and 60% for adenocarcinoma (p-value < 0.0001). In MCR models, only squamous cell carcinoma exhibited higher CSM than UCUB (HR 1.98, 95%CI 1.5−2.61, p-value < 0.001). Despite the small number of observations, squamous cell carcinoma distinguished itself from UCUB based on worse survival in T2N0M0 patients after TMT.