Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts.

BACKGROUND: This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. METHODS: From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1-6 and the second for cases 7-9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. RESULTS: The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76-0.81; mean Hmean = 2.11-3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63-0.64; mean Hmean = 5.66-7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature. CONCLUSIONS: We have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial.

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Expression of Types I and III Collagens and Ultrastructure of the Extracellular Matrix in Rectal Adenocarcinoma of Different Differentiation Degree after Neoadjuvant Radiation Therapy.

The structural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy was studied on postoperative material using immunohistochemistry and electron microscopy. The differences in the expression of types I and III collagens, as well as in the ultrastructural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy were revealed. We observed high expression of collagen I and wide channels in the collagen matrix in the central areas of the well differentiated adenocarcinomas without neoadjuvant radiation therapy and in poorly differentiated adenocarcinomas after neoadjuvant radiation therapy, which can be associated with metastasis and poor prognosis for the patients.

Predicting pathological complete response of neoadjuvant radiotherapy and targeted therapy for soft tissue sarcoma by whole-tumor texture analysis of multisequence MRI imaging.

OBJECTIVES: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients. METHODS: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T1-weighted with fat saturation and contrast enhancement (T1FSGd), T2-weighted with fat saturation (T2FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Five of 30 patients (16.7%) achieved pCR. The Delta_Model (AUC 0.92) had a better predictive ability than the Pre_Model (AUC 0.78) and Post_Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined_Model (pre, post, and delta features) had the best predictive performance (AUC 0.95). CONCLUSION: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging. KEY POINTS: • MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. • Texture features showed incremental value beyond routine clinical factors. • The Combined_Model with features at multiple time points showed the best performance.

Response Evaluation of Neoadjuvant Therapies in Sarcoma.

OPINION STATEMENT: Sarcoma is a complex and heterogeneous disease with a rapidly evolving treatment landscape. With a growing emphasis on neoadjuvant therapy as a way to improve surgical and oncologic outcomes, our approach to monitor treatment efficacy must also continue to evolve. This is paramount to both clinical trial design, where endpoints must accurately reflect disease outcomes, and individual patient, whose treatment response informs therapeutic decisions. In the era of personalized medicine, the response to neoadjuvant treatment in sarcoma remains most effectively gauged by pathologic review following surgical resection. Although measures of pathologic complete response most effectively predict outcome, the requisite surgical excision precludes their use in real-time monitoring of neoadjuvant treatment response. Current image-based metrics such as RECIST and PERCIST have been utilized in many trials; however, they are limited by their unilateral measurement approach. More effective tools are needed to better measure the response to therapy prior to neoadjuvant regimen completion, so that the medication or regimen may be best tailored to patient response in an ongoing fashion. Delta-radiomics and circulating tumor DNA (ctDNA) represent promising novel tools for real-time monitoring of treatment efficacy. These metrics have been shown to predict pathologic complete response and disease progression at a superior level to traditional CT-based guidelines. Delta-radiomics is currently being utilized in a clinical trial among soft tissue sarcoma patients in which radiation dosage is adjusted based on radiomic data. The ability of ctDNA to detect molecular residual disease is also under study in multiple clinical trials, although none in the field of sarcoma. Future directions in the field include the use of ctDNA and molecular residual disease testing among sarcoma patients, as well as increased utilization of delta-radiomics, to more effectively monitor neoadjuvant treatment response prior to surgical resection.

Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial.

BACKGROUND: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC. METHODS: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters. DISCUSSION: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.

Neoadjuvant radiation above NCCN guidelines for rectal cancer is associated with age under 50 and early clinical stage.

INTRODUCTION: Recent data suggest patients with early-onset rectal cancer (EORC) receive neoadjuvant radiation above recommended doses without oncologic benefit. The use of excessive radiation may lead to worse outcomes and patient harm. We sought to evaluate predictors of aggressive neoadjuvant radiation (A-XRT) use in EORC patients and compare this to late-onset rectal cancer (LORC) patients. METHODS: The National Cancer Database from 2004 to 2014 was queried for rectal adenocarcinoma patients undergoing surgical resection. Patients with stage 0 or IV disease, positive margins, and incomplete data were excluded. Standard neoadjuvant radiation (S-XRT) was based upon NCCN guidelines: 25-50.4 Gray for stage II/III patients and none for stage I. Excess radiation was considered A-XRT. Patients diagnosed at age < 50 years were labeled EORC; those ≥ 50 years were LORC. Categorical data were analyzed with chi-square test. Logistic regression was used to analyze clinicodemographic associations with A-XRT. RESULTS: 45,403 patients were included: 7999 (17.6%) EORC and 37,404 (82.4%) LORC. Multivariable logistic regression demonstrated that A-XRT use among stage I patient was associated with male gender, age under 50, urban location, mucinous histology, and poor tumor differentiation. Among stage II and III patients, A-XRT use was associated with male gender, age under 50, higher education and income, and urban location. Cox hazards did not demonstrate a significant association of A-XRT use with survival. CONCLUSION: Our data reaffirm that EORC patients more frequently receive A-XRT and that use is based on demographic features independent of tumor characteristics. Reasons for A-XRT, particularly in EORC patients, should be clarified to promote adherence to guidelines and minimize patient harm.

Does Timing Matter? Surgical Outcomes in High-Grade Sarcomas after Neoadjuvant Radiation Therapy.

BACKGROUND: The impact of time to surgical resection after neoadjuvant external beam radiation therapy (EBRT) in the high-grade soft tissue and retroperitoneal sarcomas has not been well established. We aimed to evaluate how surgical timing from EBRT affects oncologic and perioperative outcomes. METHODS: We performed a single institution retrospective cohort study of patients with biopsy-proven, high-grade sarcoma who completed neoadjuvant EBRT and resection from January 1, 1999 to September 1, 2018. We collected demographic and clinicopathologic variables, stratifying patients by time interval between EBRT and surgery: <6, 6-8, 8-10, and >10 wk. Primary outcomes collected were as follows: disease-free survival, overall survival, and perioperative complications. RESULTS: Of the 269 patients identified, 146 met inclusion criteria. The median follow-up was 24 mo. Overall and local recurrence were 37% (n = 54) and 14.4% (n = 21), respectively. Time to surgery did not affect recurrence (P = 0.82) or survival (P = 0.88). Positive margins (odds ratio 2.7, confidence interval 1.14, 6.51, P < 0.05) were predictive of recurrence. Primary tumor location, surgical timing, histology, and intraoperative radiation therapy were not associated with differences in recurrence. The overall complication rate was 28%, with 63% from wound infections. Fewer postoperative complications occurred in the < 6-wk cohort versus > 6-wk cohort (15% versus 38%, P < 0.05). CONCLUSIONS: We found no difference in oncologic outcomes associated with the timing of surgical resection after EBRT. Patients undergoing resection >6 wk were at higher risk for all complications without impacting wound complication rates. Future studies may include preoperative optimization of patients requiring delays in surgical planning to decrease perioperative complication rates.

Neoadjuvant strategies in resectable carcinoma esophagus: a meta-analysis of randomized trials.

BACKGROUND: The survival benefit of neoadjuvant therapy in resectable carcinoma esophagus has been elucidated. We performed a meta-analysis in light of new studies and long-term results of past trials. The search strategy was refined to include only "neoadjuvant" so that any bias by adjuvant treatment is eliminated. METHODS: A detailed search of MEDLINE, Embase, and Cochrane Library was done. Only published randomized English language trials were included. Data were categorized as neoadjuvant concurrent chemoradiation (NACRT), neoadjuvant chemotherapy (NACT), neoadjuvant radiotherapy (NART), and neoadjuvant sequential chemoradiotherapy (SCRT). Meta-analysis was done using odds ratio (OR) and 95% CI using fixed/random effects model. Heterogeneity was tested by chi-square and I2 test. Z probability calculated significant difference across subgroups. Outcomes assessed were overall survival (OS) and disease-free survival (DFS) at 3 and 5 years, respectively, mortality (30/90 day) and failures (local/systemic). RESULTS: Twenty-five randomized trials involving 5272 patients were included for quantitative analysis. NACRT was evaluated in 12 studies (2676 patients). Superior 3-year OS (OR = 0.68 CI 0.52-0.90, p = 0.007), 3-year DFS (OR = 0.55 CI 0.45-0.68, p = 0.00001), and 5-year DFS (OR = 0.59 CI 0.47-0.74, p = 0.00001), with lower failures (OR = 0.52 CI 0.37-0.73, p = 0.0001), were seen in favor of NACRT at the cost of increased perioperative mortality (OR = 1.79 CI 1.15-2.80, p = .01). However, 5-year OS (OR = 0.78 CI 0.60-0.1.01, p = 0.06) was not found to be significantly superior. NACT, NART, and SCRT were not found to have any benefit over surgery alone. CONCLUSION: This meta-analysis presents strong evidence favoring NACRT over upfront surgery. It also shows no survival advantage of neoadjuvant chemotherapy.

Health-related quality of life in locally advanced cervical cancer patients treated with neoadjuvant therapy followed by radical surgery: A single-institutional retrospective study from a prospective database.

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) in locally advanced cervical cancer (LACC) patients treated with neoadjuvant concurrent chemoradiation (CCRT) or radiation (RT) alone followed by radical surgery (RS). METHODS: In a single-center retrospective study from a prospective database, 275 FIGO Stage IB2-IIIB patients who underwent CCRT/RT + RS were included. HRQOL was prospectively assessed by EORTC QLQ-C30 and EORTC QLQ-CX24 prior to any treatment (baseline) and 6 months after surgery, respectively. RESULTS: A statistically significant and clinically relevant improvement in physical functioning (P < 0.001) and role functioning (P = 0.002, P = 0.031) was observed in patients receiving either CCRT+RS or RT + RS at follow-up. In addition, quality of life (QoL), physical functioning, and social functioning were better in the RT + RS group than the CCRT+RS group after treatment (P = 0.028, P = 0.010, P = 0.014). Symptom scores of fatigue decreased in both groups over time (P < 0.001, P = 0.004) while insomnia decreased only in the RT + RS group (P = 0.042). Worsened menopausal symptoms were documented in both groups at follow-up (P = 0.001, P = 0.047), while lymphedema was deteriorated only in patients receiving CCRT + RS (P < 0.001). Sexuality scores did not differ between groups or over time with the exception of sexual worry, which was deteriorated in patients receiving RT + RS (P = 0.042). CONCLUSIONS: QLQ-C30 functioning and tumor-related symptoms scores improved while lymphedema and menopausal symptoms worsened 6 months after neoadjuvant CCRT or RT alone followed by RS in LACC patients. Patients treated with RT + RS had a generally better HRQOL compared with those receiving CCRT+RS, though further validation with prospective randomized clinical trials is warranted.

Adaptive radiotherapy in patients receiving neoadjuvant radiation for soft tissue sarcoma.

AIM: The aim of this study is to evaluate tumor volume changes during preoperative radiotherapy and to assess the role of adaptive radiation. BACKGROUND: Contemporary neoadjuvant radiotherapy utilizes image guidance for precise treatment delivery. Moreover, it may depict changes in tumor size and shape. MATERIALS AND METHODS: Between 2016 and 2018, 23 patients aged ≥18 years with soft tissue sarcoma were treated with neoadjuvant radiation followed by surgical resection. The tumor volumes (cc) were measured using the Pinnacle planning system prior to starting radiotherapy and during treatment, the changes in volume and absolute differences were estimated. Moreover, patient's position on the machine was evaluated to assess setup offsets. The triggers for plan adaptation were >1 cm expansion or unacceptable setup offsets. RESULTS: The mean tumors volume at presentation was 810 cc (range, 55-4000). At last cone beam CT the tumor volume had changed in 14 patients (61%); it was stable in nine patients (39%). Disease regression was documented in eight patients (35%), with median shrinkage of -20.5% (range, -2 to -29%), while tumor progression was observed in six cases (26%), the median change was 12.5% (range, +10 to +25%).Adaptive radiation was required in four patients (17%). For the remaining 19 cases (83%), the dose distribution was adequate to cover target volumes. CONCLUSIONS: Change in soft tissue sarcoma volume during radiation is not uncommon. Image guidance should be used to reduce setup errors and to detect differences in tumor volume. Image guidance and adaptive radiation are paramount to ensure optimal radiation delivery.

Preoperative radiation therapy in the surgical management of gastric and junctional adenocarcinoma: Should lymph node retrieval guidelines be altered?

BACKGROUND: Although surgery remains the cornerstone of gastric cancer therapy, the use of radiation therapy (RT) is increasingly being employed to optimize outcomes. We sought to assess outcomes following use of RT for the treatment of gastric adenocarcinoma. METHODS: Using the National Cancer Data Base (NCDB) from 1998 to 2012, all patients with resected gastric adenocarcinoma were identified. Patients were stratified into four groups based on preoperative therapy: RT alone, chemotherapy only, chemoradiotherapy (CRT), and no preoperative therapy. Overall survival was estimated using multivariate Cox proportional hazards model. Adjusted secondary outcomes include margin positivity, lymph node harvest, LOS, 30-day readmission and mortality. RESULTS: A total of 10 019 patients met study criteria. In the unadjusted analysis, patients undergoing CRT compared to chemotherapy alone had fewer positive margins (7.9% vs 15.9%; P < 0.001), increased negative LNs (54.6% vs 37.7%; P < 0.001) with reduced LN retrieval (mean: 13.5 vs 19.6; P < 0.01). After multivariate adjustment, there was no survival benefit to any preoperative therapy; however, preoperative RT/CRT remained associated with decreased LN retrieval. CONCLUSIONS: The results support previous reports on preoperative RT resulting in decreased margin positivity. This study highlights the need to reconsider practice guidelines regarding appropriate lymphadenectomy in the setting of preoperative RT given reduced LN retrieval.

Neoadjuvant Short-Course Radiation Therapy for Rectal Cancer: Trends and Controversies.

PURPOSE OF REVIEW: For patients with locally advanced rectal cancer, neoadjuvant hypofractionated short-course radiation remains an underutilized regimen in the USA. We review the current clinical literature highlighting the relative merits of short-course radiation, along with modern neoadjuvant strategies that incorporate its use. RECENT FINDINGS: As compared to long-course chemoradiation with delayed surgery, short-course radiation with early surgery offers similar oncologic efficacy for locally advanced rectal cancer patients. Delaying surgery after short-course radiation decreases post-operative complications as compared to early surgery and improves tumor downstaging. Delaying surgery also offers the opportunity to administer neoadjuvant systemic therapy, which may help increase local-regional tumor response and potentially decrease distant relapse rates, the latter a persisting problem in rectal cancer treatment. Short-course radiation, either with immediate or with delayed surgery, represents an appealing treatment alternative to long-course chemoradiation for patients with locally advanced rectal cancer.

Neoadjuvant radiation therapy does not increase perioperative morbidity among patients undergoing gastrectomy for gastric cancer.

BACKGROUND: Neoadjuvant radiation therapy (RT) as a component of the multimodality treatment of gastric cancer has demonstrated promising results. Data regarding its effect on perioperative safety are limited. METHODS: Adults undergoing gastrectomy for gastric cancer in the 2005-2011 National Surgical Quality Improvement Program were included. Groups were defined by neoadjuvant RT use, and then propensity-matched based on preoperative variables. Multivariable logistic regression was performed to assess neoadjuvant RT as an independent predictor of outcomes. RESULTS: Among 2,764 patients identified, 55 (2.0%) were treated with neoadjuvant RT. Patients who received neoadjuvant RT were more likely to have received preoperative chemotherapy and steroids, and experienced weight loss (all P < 0.01). After matching, however, there were no preoperative differences. At time of surgery, total (vs. partial) gastrectomy was more common among patients who underwent neoadjuvant RT (70.9 vs. 46.7%, P < 0.01), and operative time was longer (290 vs. 236 min, P < 0.01). There were no differences in overall complications (23.6 vs. 29.7%, P = 0.49) or 30-day mortality (3.6 vs. 3.6%, P = 0.99). CONCLUSIONS: Neoadjuvant RT was not associated with increased morbidity or mortality following resection for gastric cancer. These findings support the ongoing investigation of neoadjuvant RT as part of the multidisciplinary management of resectable gastric cancer.

Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

Short-course preoperative radiotherapy (RT) is widely used in northern Europe for locally advanced resectable rectal cancer, but its role in the era of advanced imaging techniques is uncertain. Here, we reviewed articles and abstracts on SCRT published from 1974 through 2013 with the goal of identifying patients who might be best suited for short-course RT. We included relevant articles comparing surgery with or without preoperative radiation published before and after the advent of total mesorectal excision. We also analyzed two randomized trials directly comparing short-course RT with conventionally fractionated chemoradiation (the Polish Colorectal Study Group and the Trans-Tasman Radiation Oncology Group) that compared short-course RT with conventional chemoradiotherapy. We conclude from our review that short-course RT can be generally applied for operable rectal cancer and produces high rates of pelvic control with acceptable toxicity; it reduces local recurrence rates but does not increase overall survival. SCRT seems to be best used for tumors considered "low risk," i.e., those that are >5 cm from the anal margin, without circumferential margin involvement, and involvement of fewer than 4 lymph nodes. Whether sequential chemotherapy can further improve outcomes remains to be seen, as does the best time for surgery (immediately or 6-8 weeks after RT). We further recommend that selection of patients for short-course RT should be based on findings from magnetic resonance imaging or transrectal ultrasonography.

Preoperative radiation for retroperitoneal sarcoma is not associated with increased early postoperative morbidity.

BACKGROUND AND OBJECTIVES: Preoperative radiation (PR) in the management of retroperitoneal sarcoma (RPS) is controversial. Concern for increased perioperative morbidity may influence the decision to recommend PR. Here we compare 30-day morbidity and mortality (M + M) after resection of RPS with and without PR. METHODS: Patients undergoing resection of RPS were identified using ACS NSQIP (2005-2011). Patients with known PR status within 90 days of operation were included. Univariate and multivariate logistic regression analyses were performed to identify factors associated with M + M. RESULTS: Of 696 patients operated on for RPS, 70 (10%) underwent PR. PR patients were younger (mean 55 vs. 61 years), more frequently had hypoalbuminemia (<3 g/dl; 19% vs. 10%), concomitant kidney (29% vs. 18%), or pancreas resections (11% vs. 5%), longer operations (mean 327 vs. 253 min), and increased transfusion requirements (mean 4.1 vs. 2.1 units, each P < 0.05). Despite these differences, the M + M rate (31% with vs. 30% without PR, P = 0.75) was comparable between the two groups. After adjustment for confounders, no association was identified between PR and M + M. CONCLUSIONS: In a national cohort of RPS patients, PR is infrequently utilized. Despite the increased prevalence of multiple risk factors, PR patients do not have an increased 30-day postoperative M + M.

A Review of Neoadjuvant Therapy and the Watch-and-Wait Protocol in Rectal Cancer: Current Evidence and Future Directions.

The treatment of rectal cancer underwent a significant change with the introduction of total mesorectal excision (TME), which substantially improved recurrence rates. However, TME is associated with complications such as fecal incontinence and poor bladder control, especially in tumors located near the anal verge. The watch-and-wait (WW) protocol has emerged as an alternative for patients achieving a clinical complete response (cCR) following neoadjuvant radiochemotherapy. This narrative review, developed according to the Scale for the Assessment of Narrative Review Articles guidelines, evaluates neoadjuvant treatments and the WW protocol for rectal cancer. Literature was sourced from the PubMed database using specific search terms related to neoadjuvant therapy and the WW protocol, resulting in 63 articles selected for discussion. Neoadjuvant treatment, including chemoradiation and short-course radiotherapy, is indicated for T3 and T4 rectal adenocarcinomas. Studies like the German Rectal Cancer Study Group and the PRODIGE 23 trial have shown the benefits of preoperative treatment, including improved disease-free survival and reduced local recurrence rates. However, challenges in adopting the WW protocol include the risk of local regrowth and distant metastasis. Immune checkpoint inhibitors have shown promise in mismatch repair-deficient patients, yet the data are insufficient to fully endorse WW for these cases. The WW protocol is viable for selected rectal cancer patients, with ongoing debates regarding criteria for inclusion. Key challenges include accurately identifying cCR and managing patients with near-complete responses. MRI and endoscopic evaluation are crucial for assessing treatment response, although achieving a pathological complete response remains uncertain. The WW strategy offers a potential organ-preserving approach in rectal cancer management but requires careful patient selection and comprehensive risk-benefit discussions. Further research is needed to refine criteria for inclusion and optimize treatment protocols, enhancing outcomes while minimizing invasive interventions.

Impact of preoperative radiation on survival of patients with T3N0 >7-cm non-small cell lung cancers treated with anatomic resection using the Surveillance, Epidemiology, and End Results database.

BACKGROUND: Very large non-small cell lung cancers (NSCLC) remain a therapeutic challenge. The objective of this study was to evaluate the effect of surgery in the presence and absence of neoadjuvant radiation (NRT) on survival of patients with T3N0 >7-cm NSCLCs. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients undergoing lobectomy or pneumonectomy for T3N0 NSCLC tumors >7 cm from 1999-2008. Patients were categorized into groups based on type of surgery performed and whether NRT was used. Five-year overall (OS) and lung cancer-specific survival (LCSS) were estimated by the Kaplan-Meier method and comparisons made using log-rank tests and Cox regression models. RESULTS: There were 1301 patients evaluated, including 1232 undergoing primary surgical therapy (PST) and 69 receiving NRT. NRT was not associated with improvements in 5-y OS (48% versus 41%, P = 0.062) or LCSS (59% versus 52%, P = 0.116) compared with PST. Lobectomies were associated with better 5-y OS (43% versus 33%; P = 0.006) and LCSS (54% versus 43%, P = 0.005) compared with pneumonectomies. On multivariate analysis, NRT did not produce any significant advantage in OS (P = 0.242) and LCSS (P = 0.208). Pneumonectomies were associated with significantly worse OS (hazard ratio, 1.32; P = 0.007) and LCSS (hazard ratio, 1.38; P = 0.005) when compared with lobectomies. CONCLUSIONS: NRT, which most likely was a combination of chemotherapy and radiation, was not associated with improvements in OS or LCSS in patients with T3N0 >7-cm NSCLC compared with PST. When feasible, lobectomy appears more beneficial than pneumonectomy in terms of long-term survival for very large tumors.

Data Dissemination of the Role of Neoadjuvant Radiation in Retroperitoneal Sarcoma: A CTOS and CSSO Survey.

Consensus guidelines call for complete resection of retroperitoneal sarcoma with consideration of neoadjuvant radiation for curative-intent treatment. The 15-month delay from the initial presentation of an abstract to the final publication of the STRASS trial results assessing the impact of neoadjuvant radiation led to a dilemma of how patients should be managed in the interim. This study aims to (1) understand perspectives regarding neoadjuvant radiation for RPS during this period; and (2) assess the process of integrating data into practice. A survey was distributed to international organizations including all specialties treating RPS. Eighty clinicians responded, including surgical (60.5%), radiation (21.0%) and medical oncologists (18.5%). Low kappa correlation coefficients on a series of clinical scenarios querying individual recommendations before and after initial presentation as an abstract indicate considerable change. Over 62% of respondents identified a practice change; however, most also noted discomfort in adopting changes without a manuscript available. Of the 45 respondents indicating discomfort with practice changes without a full manuscript, 28 (62%) indicated that their practice changed in response to the abstract. There was substantial variability in recommendations for neoadjuvant radiation between the presentation of the abstract and the publication of trial results. The difference in the proportion of clinicians describing comfort with changing practice based on the presentation of the abstract versus those that had done so shows that indications for proper integration of data into practice are not clear. Endeavors to resolve this ambiguity and expedite availability of practice-changing data are warranted.