UNASSIGNED: The aim of this retrospective analysis was to determine if the response to preoperative radio(chemo)therapy is predictive for survival among patients with locally advanced rectal cancer and may act as a potential surrogate endpoint for disease free survival and overall survival.
UNASSIGNED: Eight hundred seventy-eight patients from five centers were analyzed. There were 304 women and 574 men; the median age was 64.7 years. 77.6% and 22.4% of patients received neoadjuvant radiochemotherapy or short-course radiotherapy, resulting in a pathological complete response in 7.3%. T-downstaging and N-downstaging occurred in 50.5% and 37% of patients after neoadjuvant therapy. In patients with T-downstaging, the 10-year DFS and 10-year OS were 64.8% and 66.8% compared to 37.1% and 45.9% in patients without T-downstaging. N-downstaging resulted in 10-year DFS and 10-year OS in 56.2% and 62.5% compared to 47.3% and 52.3% without N-downstaging. Based on routinely evaluated clinical parameters, an absolute risk prediction calculator was generated for 5-year disease-free survival, and 5-year overall survival.
UNASSIGNED: T-downstaging and N-downstaging after neoadjuvant radiochemotherapy or short-course radiotherapy resulted in better DFS and OS compared to patients without response. Based on clinical parameters, 5-year DFS, and 5-year OS can be predicted using a prediction calculator.

OBJECTIVE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI.
METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR.
RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results.
CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline \"Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1\" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.

BACKGROUND: Total neoadjuvant therapy (TNT) is a new strategy combining neoadjuvant therapy and chemotherapy to enhance tumor shrinkage and systemic control. Its effectiveness remains debated.
OBJECTIVE: This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess TNTs impact and provide high-quality evidence for rectal cancer treatment decisions.
METHODS: We searched China National Knowledge Infrastructure, VIP Database, Wanfang Database, China biomedical literature database, PubMed database, Embase database, and The Cochrane Library for RCTs comparing TNT with neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. The included trials were screened and assessed for quality based on inclusion and exclusion criteria, and meta-analysis was performed using RevMan 5.3 software.
RESULTS: A total of 11 RCTs reported in 14 articles, with 1,624 cases in the TNT group and 1,541 cases in the CRT group. The results of the meta-analysis showed that compared with the CRT group, the TNT group had a higher pathological complete response rate (risk ratio [RR] = 1.65, 95% confidence interval [CI]: [1.40, 1.94], p < 0.00001), higher T0 downstaging rate (RR = 1.51, 95% CI: [1.29, 1.77], p < 0.00001), higher 3-year overall survival (hazard ratio [HR] = 0.81, 95% CI: [0.67, 0.98], p = 0.03), and higher 3-year disease-free survival (HR = 0.82, 95% CI: [0.70, 0.95], p = 0.008). However, there was no statistically significant difference between the two groups in terms of R0 resection rate (RR = 1.02, 95% CI: [0.99, 1.05], p = 0.14), sphincter preservation rate (RR = 0.94, 95% CI: [0.88, 1.01], p = 0.12), anastomotic leakage rate (RR = 1.42, 95% CI: [0.85, 2.38], p = 0.18), and grade 3 or higher adverse events (RR = 1.21, 95% CI: [0.95, 1.54], p = 0.13).
CONCLUSIONS: In the treatment of locally advanced rectal cancer, TNT offers greater survival benefits compared to neoadjuvant CRT and does not significantly increase the incidence of adverse events. However, further data and studies with long-term outcomes are still required.

The management of locally advanced rectal cancer (LARC) suffered changes thanks to the development of improved surgical procedures, radiation delivery, and chemotherapy. Although treatment options improved individually, the optimal order is still debated. Neoadjuvant chemo-radiotherapy followed by total mesorectal excision (TME) has been the \"golden standard\" for locally advanced rectal cancer. There is no common ground in international guidelines on the indications of adjuvant chemotherapy (ADJCHT), with differences between the American, European, and Japanese guidelines. This paper studies the preferences of Romanian oncologists in prescribing ADJCHT. We conducted a single-institution, retrospective study of all nonmetastatic, ECOG 0-1 LARC patients staged II-III who underwent TME and were admitted to the Oncology or Radiotherapy Department of Colțea Clinical Hospital, Bucharest between January 2017 and March 2021. A total of 186 patients were included in the study. A positive correlation was found between ADJCHT and each of the following: (y)pT > 2, (y)pN > 0, and the presence of perineural invasion (PNI+). A strong positive correlation was found between ADJCHT and the presence of at least one risk factor: (y)pT > 2, (y)pN > 0, PNI+, lymphovascular invasion, positive margins, or tumor grade > 1. Tumor downstaging decreased the risk of metastases in the first 2 years and was associated with the use of neoadjuvant radiotherapy, while adding neoadjuvant chemotherapy increased the chance of nodal downstaging. ADJCHT practice for LARC in Romania follows either NCCN or ESMO guidelines, at the discretion of the oncologist, due to the lack of national guideline.

BACKGROUND: The question of the ideal neoadjuvant therapy for locally advanced esophagogastric adenocarcinoma has not been answered to date. Multimodal treatment has become a standard treatment for these adenocarcinomas. Currently, perioperative chemotherapy (FLOT) or neoadjuvant chemoradiation (CROSS) is recommended.
METHODS: A monocentric retrospective analysis compared long-term survival after CROSS versus FLOT. The study enrolled patients with adenocarcinoma of the esophagus (EAC) or the esophagogastric junction type I or II undergoing oncologic Ivor-Lewis esophagectomy between January 2012 and December 2019. The primary objective was to determine the long-term outcome in terms of overall survival. The secondary objectives were to determine differences regarding the histopathologic categories after neoadjuvant treatment and the histomorphologic regression.
RESULTS: The findings showed no survival advantage for one or the other treatment in this highly standardized cohort. All the patients underwent open (CROSS: 9.4% vs. FLOT: 22%), hybrid (CROSS: 82% vs. FLOT: 72%), or minimally invasive (CROSS: 8.9% vs. FLOT: 5.6%) thoracoabdominal esophagectomy. The median post-surgical follow-up period was 57.6 months (95% confidence interval [CI] 23.2-109.7 months), and the median survival was longer for the CROSS patients (54 months) than for the FLOT patients (37.2 months) (p = 0.053). The overall 5-years survival was 47% for the entire cohort (48% for the CROSS and 43% for the FLOT patients). The CROSS patients showed a better pathologic response and fewer advanced tumor stages.
CONCLUSIONS: The improved pathologic response after CROSS cannot be translated into longer overall survival. To date, the choice of which neoadjuvant treatment to use can be made only on the basis of clinical parameters and the patient\'s performance status.

BACKGROUND: Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins, including growth-hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL, in specimens of locally advanced rectal cancer patients, as well as the time to metastasis and 10-year overall survival (OS) rates. We also investigated whether these outcome measures were associated with the presence of other clinical parameters.
METHODS: In total, 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for the proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationships between the intensity of expression of biomarkers, clinical parameters, the time to metastasis and the 10-year OS rate.
RESULTS: High levels of p-Akt, GHRH-R and Hsp90 were associated with a significantly decreased 10-year OS rate (p = 0.001, p = 0.000, p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with a significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both a significantly longer time to metastasis and an improved 10-year OS rate.
CONCLUSIONS: Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of the 10-year OS rate in locally advanced rectal cancer patients. The GHRH-R and Hsp90 expression levels were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for the anticancer treatment of advanced rectal cancer.

This study aimed to evaluate the benefit of additional administration of oxaliplatin during fluorouracil-based neoadjuvant radiochemotherapy (nRCT) in terms of pathologic complete remission (pCR), disease-free survival (DFS), and overall survival (OS) in patients with advanced rectal cancer. Between 2006 and 2021, 669 patients (pts) were diagnosed with locally advanced rectal cancer, of whom a total of 414 pts with nRCT were identified and included in the study. A total of 283 pts were treated by nRCT using concurrent chemotherapy with fluorouracil or capecitabine; 131 pts were treated using a combination of fluorouracil or capecitabine and oxaliplatin. Propensity score matching analyses (PSM) with 114 pts in each group were used to balance the patients\' characteristics. OS, DFS, pCR-rate, and potential prognostic factors were compared between the two groups. The median follow-up time was 59.5 weeks in the fluorouracil-group and 43 weeks in the fluorouracil/oxaliplatin group (p = 0.003). After PSM, the pCR-rate (including sustained clinical complete remission) was 27% (31/114 pts) in the fluorouracil/oxaliplatin group and 16% (18/114 pts) in the fluorouracil-group (p = 0.033). There was no difference between these two groups for both 10-year OS and DFS neither before nor after PSM, respectively (OS: 72.6% vs. 55.4%, p = 0.066, and 67.8% vs. 55.1%, p = 0.703, and DFS: 44.8% vs. 46.8%, p = 0.134, and 44.7% vs. 42.3%, p = 0.184). Multivariate analysis identified regression grading according to Dworak grade 4 (HR: 0.659; CI: 0.471-0.921; p = 0.015) and age over 60 years (HR: 2.231; CI: 1.245-4.001; p = 0.007) as independent predictors for OS. In conclusion, the addition of oxaliplatin to fluorouracil during nRCT significantly improved pCR-rate without having an impact on survival.

To assess oncological outcomes of patients receiving neoadjuvant radiochemotherapy (RCT) for soft tissue sarcoma (STS) of the extremities.
Patients who were treated with preoperative radiotherapy and concomitant chemotherapy-3 cycles of mitomycin/doxorubicin/cisplatin (MAP) or 2-4 cycles of doxorubicin/cisplatin (AP)-followed by surgery were analyzed retrospectively. Survival rates were estimated, and prognostic factors were identified.
Between 1994 and 2017, a total of 108 patients were included. Median ages were 43 years and 51 years for patients receiving MAP and AP, respectively. The 5‑year local relapse-free survival (LRFS), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were 94.1, 63.6, 75.3, and 71.9%, respectively. In the multivariate analysis, significant predictors were identified as follows: de novo or R1/R2 resected tumor on admission before RCT (p = 0.017; hazard ratio [HR] 0.112, 95% confidence interval [CI] 0.019-0.675) and R0 resection after RCT (p = 0.010; HR 0.121, 95% CI 0.024-0.598) for LRFS; female gender (p = 0.042; HR 0.569, 95% CI 0.330-0.979) and liposarcoma histology (p = 0.014; HR 0.436, 95% CI 0.224-0.845) for DFS; liposarcoma histology (p = 0.003; HR 0.114, 95% CI 0.027-0.478) and AP regimen (p = 0.017; HR 0.371, 95% CI 0.165-0.836) for DSS; age ≤ 45 years (p = 0.043; HR 0.537, 95% CI 0.294-0.980) and liposarcoma histology (p = 0.006; HR 0.318, 95% CI 0.141-0.716) for OS, respectively.
An increased risk for local failure seems to exist for patients with relapsed tumor on admission and having positive surgical margins after neoadjuvant RCT. Intensity of chemotherapy influenced DSS but not OS, which could be due to younger patients receiving MAP.

Radiation therapy represents, together with surgery and systemic treatment, the triad on which the current management of patients with breast cancer is based, achieving high control and survival rates. In recent years we have witnessed a (r)evolution in the conception of breast cancer treatment. The classic scheme of surgery followed by systemic treatment and radiotherapy is being subverted and it is becoming more and more frequent to propose the primary administration of systemic treatment before surgery, seeking to maximize its effect and favoring not only the performance of more conservative surgeries but also, in selected cases, increasing the rates of disease-free survival and overall survival. Radiotherapy is also evolving toward a change in perspective: considering preoperative primary administration of radiotherapy may be useful in selected groups. Advances in radiobiological knowledge, together with technological improvements that are constantly being incorporated into clinical practice, support the administration of increasingly reliable, precise, and effective radiotherapy, as well as its safe combination with antitumor drugs or immunotherapy in the primary preoperative context. In this paper, we present a narrative review of the usefulness of preoperative radiotherapy for breast cancer patients and the possibilities for its combination with other therapies.