Dosimetric comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy for free-breathing whole-breast irradiation: A planning study.

Background: Currently, recommended heart dose constraints are difficult to meet in whole-breast irradiation (WBI) for left-sided breast cancer patients, who cannot be treated with the deep inspiration breath hold. We performed a radiotherapy planning study to establish if the use of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) allows for better sparing of the heart and its subvolumes than the three-dimensional conformal radiation therapy (3D-CRT), and how these attempts affect the dose delivered to the other organs. Methods: A total of 17 left-sided and 10 right-sided consecutive patients treated with free-breathing WBI were retrospectively included. The 3D-CRT, IMRT, and VMAT plans were generated. Several dose-volume parameters and plan quality indices were compared, separately for the left- and right-sided plans. Results: All the techniques fulfilled the planning objectives. In the left-sided plans, there was no heart or left ventricle dose reduction with IMRT, nor with VMAT; the maximum dose in the left anterior descending coronary artery was reduced with VMAT (P = 0.005); V5 for the contralateral breast, contralateral lung, and total-body increased markedly in VMAT, and for the ipsilateral lung (V5IL) also in IMRT, compared with 3D-CRT (P < 0.001). In the right-sided plans, the V5 values, except for V5IL, did not differ between the three techniques. Conclusions: IMRT and VMAT had a limited heart-sparing benefit in the left-sided free-breathing WBI, at the cost of increased low-dose volumes, measured by V5. The low-dose volumes are not increased by IMRT or VMAT in the right-sided WBI, where heart sparing is not a problem, but the attempts to reduce cardiac doses in the left-sided WBI increase them.

Five-year follow-up after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer: a multicenter study.

Background: Stereotactic body radiotherapy (SBRT) has proven to provide high rates of tumor control for patients with early-stage non-small cell lung cancer (NSCLC). We are reporting a multicenter experience of long-term clinical outcomes and adverse effect profiles of patients with medically inoperable early-stage NSCLC treated with SBRT. Methods: A total of 145 early-stage NSCLC patients underwent SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Shandong Cancer Hospital and Institute, and Shanghai Pulmonary Hospital between October 2012 and March 2019. Four-dimensional computed tomography (4D-CT) simulation was used for all patients. All received a biologically effective dose (BED; α/ß=10) of 96-120 Gy with the prescribed isodose line covering >95% of the planning target volume (PTV). Survival was analyzed by the Kaplan-Meier method. Survival was estimated using the Kaplan-Meier method. Results: The median tumor diameter was 2.2 (range, 0.5-5.2) cm. The median follow-up was of 65.6 months. Thirty-five patients (24.1%) developed disease recurrence. The rates of local, regional, and distant disease recurrence were, respectively, 5.1%, 7.4%, and 13.2% at 3 years; and 9.6%, 9.8%, and 15.8% at 5 years. Progression-free survival (PFS) rates at 3 and 5 years were 69.2% and 60.5% respectively; the overall survival (OS) rates were 78.1% and 70.1%, respectively. Five patients (3.4%) experienced grade 3 treatment-related adverse events (AEs). No patient experienced grade 4 or 5 toxicity. Conclusions: From our retrospective analysis with long-term follow-up in Chinese population, SBRT achieved high rate of local control (LC) and low toxicity in patients with early-stage NSCLC. This study offered robust long-term outcome data of SBRT in the Chinese population, which was very rarely reported in China before.

Re-Whole Brain Radiotherapy for Brain Metastases: How to Evaluate an Outcome of Repeat Treatment When Its First Use Is Debatable.

Recently, a review on a pertinent issue of repeat whole-brain radiotherapy (re-WBRT) for recurring brain metastases was published [...].

Palliative extracranial radiotherapy in patients receiving immunotherapy for non-small cell lung cancer: a narrative review.

Background and Objective: Role of radiotherapy (RT) in the era of immuno-oncology (IO) in advanced non-small cell lung cancer (NSCLC) is rapidly changing. RT is not only intended for addressing palliation symptoms but also is considered as a potential tool potentializing an immunogenic effect of given drugs. However, the best timing, techniques, doses, volumes, and its use for asymptomatic patients is a subject of research. We performed a review on the role of palliative RT schedules in combination with IO for advanced NSCLC. Indications in symptomatic and asymptomatic patients, outcomes, toxicity, and possible developments are discussed. Methods: A literature search was conducted in MEDLINE and PubMed databases and clinicaltrials.gov using the keywords 'lung cancer' AND "immunotherapy" AND 'radiotherapy' OR "palliative radiotherapy". Key Content and Findings: Body of evidence indicate that palliative RT used in combination with IO is effective in terms of symptom management and safe; does not increase the risk of serious side effects, including serious pulmonary toxicity. We have limited data evidencing improvement of survival by addition of short ablative RT dose to one site of the disease to IO in oligometastatic NSCLC. Some data indicate that short ablative doses of stereotactic body radiation therapy (SBRT) are more effective with regard to treatment response and survival than protracted RT schedule with lower fractional doses. However, this may be a selection bias of better prognostic patients who underwent SBRT. The use of steroids being a potential concern during IO should not be prohibited if clinically indicated during palliative RT. Its detrimental effect shown in some studies may also be a result of selection bias, because steroids given for not cancer-related causes during IO did not decrease survival. Conclusions: RT for symptom management may be used during, directly before or after IO. This has a potential to ease symptom burdens and improve performance status (PS). However, still more studies are needed to establish optimal guidelines in asymptomatic patients for appropriate timing, volumes, dose, and fractionation schedules of palliative RT use in combination with IO.

International consensus on radiotherapy in metastatic non-small cell lung cancer.

Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease. Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide. Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions: In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

A nomogram to predict the recurrence-free survival and analyze the utility of chemotherapy in stage IB non-small cell lung cancer.

BACKGROUND: Large part of patients of stage IB non-small cell lung cancer (IB NSCLC) may suffer recurrence after surgery. This study is to determine risk factors and establish a nomogram for postoperative recurrence and to provide a reference for adjuvant chemotherapy selection in patients with stage IB NSCLC. METHODS: A total of 394 patients with postoperative stage IB NSCLC who visited Fujian Medical University Union Hospital between January 2010 and June 2016 were selected. Patients were divided into training and validation cohorts based on the time of diagnosis. Independent risk factors were identified using a Cox proportional hazards regression model. A nomogram was created to predict recurrence-free survival (RFS) and was validated with an independent cohort. The predictive ability of the nomogram was evaluated using the concordance index (C-index) and calibration curve. RFS between the high- and low-risk groups was determined using Kaplan-Meier curves, and subgroup analysis of chemotherapy was performed. RESULTS: Visceral pleura invasion, micropapillary structures, tumor size, preoperative serum carcinoembryonic antigen (CEA) level, preoperative serum cytokeratin-19 fragments (Cyfra21-1) level, and postoperative histology were identified as independent risk factors for stage IB NSCLC recurrence. Discrimination of the nomogram showed good prognostic accuracy and clinical applicability, with a C-index of 0.827 and 0.866 in the training and validation cohorts, respectively. The difference in RFS between the high- and low-risk groups in both cohorts was significant (P<0.05). Finally, a significant difference was observed on whether high-risk group should accept postoperative chemotherapy (P<0.05). CONCLUSIONS: This nomogram can predict postoperative recurrence probability in patients with stage IB NSCLC, and can select patients with risk factors who need adjuvant chemotherapy.

Contouring cardiac substructures on average intensity projection 4D-CT for lung cancer radiotherapy: A proposal of a heart valve contouring atlas.

BACKGROUND AND PURPOSE: A detailed contouring atlas of the heart valves is lacking. Existing heart contouring atlases have not been evaluated on average intensity projection four-dimensional non-contrast computed tomography (AVE-4D-CT) scans, routinely used for organ-at-risk delineation in lung cancer radiotherapy. We aimed to develop the heart valve contouring atlas and to assess inter-observer variation in delineation of the heart, its substructures, and coronary arteries on AVE-4D-CT scans, along with its impact on radiotherapy doses. MATERIALS AND METHODS: A heart valve contouring atlas was developed. Five radiation oncologists and four cardiologists delineated the valves according to this atlas, and the remaining heart substructures according to the existing atlases, on AVE-4D-CT scans of ten patients who underwent radio(chemo)therapy for NSCLC. The observer contours were then compared to the collectively defined "reference" contours. Spatial variation was assessed using the Sørensen-Dice similarity coefficient (DSC), directed average Hausdorff distance (DAH), directed Hausdorff distance (HD), and the mean distance to agreement (MDA). The effect of spatial variation on radiotherapy doses was assessed using the patients' treatment plans. RESULTS: Inter-observer contour overlap (mean DSC) was 0.68, 0.49, 0.45 and 0.45, and inter-observer contour separation (mean DAH) was 2.1, 3.4, 2.6 and 2.9 mm for the pulmonic (PV), aortic (AV), mitral (MV) and tricuspid valve (TV), respectively. Mean HD was higher for TV and MV (13.3 and 11.7 mm) than for AV and PV (7.8 and 7 mm). The highest mean MDA of 3.1 mm was found for AV, and the lowest (1.9 mm) for PV. Inter-observer agreement was the lowest for the coronary arteries, but statistically significant dose variation was found mainly in the left ventricular septal and anterior segments. CONCLUSION: Our atlas enables reproducible delineation of the heart valves. Delineation of the heart and its substructures on AVE-4D-CT scans is feasible, with inter-observer variability similar to that reported on conventional non-contrast CT scans.

Duration of acute esophageal toxicity in concomitant radio-chemotherapy for non-small cell lung cancer with different fractionation schedules.

OBJECTIVES: In our previous prospective trial on accelerated hypofractionated concomitant radiochemotherapy (AHRT-CHT) for non-small-cell lung cancer (NSCLC), the incidence of grade ≥3 acute esophageal toxicity (AET) was similar to that reported for conventionally fractionated concomitant radiochemotherapy (CFRT-CHT), but its duration was prolonged. Thus, we aimed to compare the duration of grade ≥3 AET between AHRT-CHT and CFRT-CHT. METHODS: Clinical data of 76 NSCLC patients treated with CFRT-CHT (60-66 Gy/2 Gy) during 2015-2020 were retrospectively compared with the data of 92 patients treated with AHRT-CHT (58.8 Gy/2.8 Gy) in the prospective trial. The maximum grade of AET, incidence, and duration of grade ≥3 AET were the end points. Univariate and multivariate analyses were applied to correlate clinical and treatment variables with these end points. RESULTS: Neither the maximum grade of AET (p = 0.71), nor the incidence of grade ≥3 AET (p = 0.87) differed between the two groups. The number of CHT cycles delivered (2 vs 1, p = 0.005) and higher esophagus mean BED (p = 0.009) were significant predictors for a higher maximum grade of AET; older age was a significant predictor for higher incidence of grade ≥3 AET (p = 0.03). The median duration of grade ≥3 AET in AHRT-CHT and CFRT-CHT group was 30 days (range 5-150) vs 7 days (range 3-20), respectively, p = 0.0005. In multivariate analysis, only the AHRT-CHT schedule (p=0.003) was a significant predictor for a longer duration of grade ≥3 AET. CONCLUSION: Despite similar incidence of grade ≥3 AET, its duration is significantly prolonged in NSCLC patients treated with AHRT-CHT compared to CFRT-CHT. ADVANCES IN KNOWLEDGE: Reporting only the rate of grade ≥3 AET in clinical trials may underestimate the real extent of the esophageal toxicity; its duration should also be routinely reported.

Radiotherapy for brain metastases from small-cell lung cancer in distinct clinical indications and scenarios.

Management of brain metastases (BM) from small-cell lung cancer (SCLC) is complex and not supported by a strong evidence from prospective clinical trials. Owing to the different clinical and pathological characteristics of SCLC, patients with this histology were not included in the prospective studies on the value of whole-brain radiotherapy (WBRT) and local surgical or ablative radiation treatment like stereotactic radiosurgery (SRS). Chemotherapy also represents a major part of the armamentarium against BM from SCLC due to the well-recognized chemoresponsiveness of this cancer and the frequent presentation of BM with extracranial progression. WBRT in combination with chemotherapy has long been a standard approach in this setting. However, data on the neurocognitive toxicity and the lack of documented impact on overall survival of WBRT in the management of BM from other solid tumors, as well as the increasing availability of the stereotactic radiotherapy technologies, has led to the increasing use of SRS with omission of WBRT also in SCLC. In the current review the use of different modalities of radiotherapy and ways of combining radiotherapy with chemotherapy for BM from SCLC will be presented for distinct clinical situations: presentation of BM synchronous with primary, metachronous presentation of BM-without previous prophylactic cranial irradiation (PCI) vs. after PCI, and asymptomatic BM found at the staging before PCI.

Prophylactic cranial irradiation in non-small cell lung cancer: evidence and future development.

In non-small cell lung cancer (NSCLC) brain metastases (BM) will affect up to 50% of patients during whole disease period. BM themselves impact heavily not only on patient's prognosis but also are a source of symptoms aggravating quality of life. Standard (pemetrexed), and non-standard chemotherapy (temozolomide) in patients with NSCLC failed to prevent them from BM. In terms of systemic treatment there are promising results showed when durvalumab (PACIFIC study), osimertinib (FLAURA trial) or alectinib (JALEX study) was used. However, those substances are effective only in small cohort with ALK or EGFR alterations. Prophylactic cranial irradiation (PCI) as a non-specific treatment has proven to be a powerful tool in preventing BM without affecting overall survival in neither way. That has been proved in nearly all earlier and all recent studies-NVALT11/DLCRG-02, RTOG 0214 update, Li et al. The positive effect of BM incidence reduction may draw fear form PCI usage due to potential cognitive toxicity the PCI may cause. Results of recent trials show that after PCI only mild cognitive disorders (MCD) may arise. Promising results in terms of reducing MCD are shown when memantine is used or/and hippocampal avoidance techniques are implemented. HA in PCI seem to be cost effective but calculations were made on small-cell lung cancer cohorts. Still even recent studies did not clarify finally which patients could benefit from PCI or other forms of preventing BM. It seems that new trials should focus on younger, fit and non-squamous histology patients and use the tests for mild cognitive disorders (MoCA, BHA) rather than screening tests for dementia (MMSE, HVLT, ADL). The main obstacle in performing new trials on PCI in NSCLC cohorts may be, however, patients' accrual, as a difficulty which occurred during latest trials.

Management of brain metastases in elderly patients with lung cancer.

The incidence of brain metastases (BM) is continuing to grow in the elderly population with lung cancer, but these patients are seriously under-represented in clinical trials. Thus, their treatment is not based on the evidence from randomized prospective studies. Age is a well recognized poor prognostic factor for survival in patients with BM from lung cancer, which is reflected in prognostic scales, but its impact on the patients' prognosis reflected by its value in gradually updated grading indices seems to decrease. The reason for poorer outcomes in the elderly is unknown-it may result from the influence of the age per se, simplified staging work-up and suboptimal treatment in this patient subgroup or the excess toxicity of the aggressive anticancer treatment secondary to the impaired physiological regulation mechanisms and comorbidities. The main goal of treatment of BM is to ameliorate neurological symptoms and delay neurological progression, with the focus on the improvement and maintenance of the patients' quality of life. The possible treatment options for BM from lung cancer are whole-brain radiotherapy, stereotactic radiosurgery, surgery, chemotherapy, targeted therapies and best supportive care. The aim of this review is to summarize the problems related to the management of BM in elderly patients with lung cancer, to analyze the value of the above mentioned treatment options, and to provide an insight into the influence of age-related clinical factors on the patients' outcomes.

Dose and fractionation schedules in radiotherapy for non-small cell lung cancer.

In the field of radiotherapy (RT), the issues of total dose, fractionation, and overall treatment time for non-small cell lung cancer (NSCLC) have been extensively investigated. There is some evidence to suggest that higher treatment intensity of RT, when given alone or sequentially with chemotherapy (CHT), is associated with improved survival. However, there is no evidence that the outcome is improved by RT at a higher dose and/or higher intensity when it is used concurrently with CHT. Moreover, some reports on the combination of full dose CHT with a higher biological dose of RT warn of the significant risk posed by such intensification. Stereotactic body radiotherapy (SBRT) provides a high rate of local control in the management of early-stage NSCLC through the use of high ablative doses. However, in centrally located tumors the use of SBRT may carry a risk of serious damage to the great vessels, bronchi, and esophagus, owing to the high ablative doses needed for optimal tumor control. There is a similar problem with moderate hypofractionation in radical RT for locally advanced NSCLC, and more evidence needs to be gathered regarding the safety of such schedules, especially when used in combination with CHT. In this article, we review the current evidence and questions related to RT dose/fractionation in NSCLC.

Should Short-Course Neoadjuvant Radiation Therapy Be Applied for Low-Lying Rectal Cancer? A Systematic Review and Meta-Analysis of the Randomized Trials.

PURPOSE: National Comprehensive Cancer Network guidelines recommend either long-course chemoradiation (LC) or short-course radiation (SC, 5 × 5 Gy) for rectal cancer before total mesorectal excision. However, they do not recommend SC for low-lying tumors. As early toxicity of SC is lower than that of LC, and postoperative complications as well as late toxicity are similar, the probable reason is a notion that for low-lying tumors LC may be more effective than SC in assuring local control. METHODS AND MATERIALS: A systematic review and meta-analysis of the randomized trials comparing SC with LC was performed to test the hypothesis that for low-lying tumors, LC is superior to SC in reducing the risk of local failure. RESULTS: The systematic search identified 4 trials including, in total, 421 patients with tumors <5 cm from the anal verge; 221 were randomized to SC and 200 to LC. The meta-analysis showed that the difference in local failure rate between SC and LC was insignificant; the pooled odds ratio was 0.87, 95% confidence interval 0.53 to 1.44, P = .59. Heterogeneity between trials was insignificant; I2 = 0.0%, P = .47. CONCLUSIONS: Our meta-analysis does not support the notion that LC given before total mesorectal excision is superior to SC in reducing the risk of local failure in low-lying tumors.

Postoperative radio-chemotherapy for rectal cancer: A retrospective analysis from a tertiary referral hospital.

AIM: To report results of postoperative radio-chemotherapy (RT-CHT) for rectal cancer (RC). BACKGROUND: Total mesorectal excision (TME) is an essential treatment method in rectal cancer (RC). Perioperative radiotherapy in locally advanced RC improves loco-regional free survival (LRFS). Preoperative radiotherapy is a preferred option; however, some patients are not referred for it. In case of the risk of loco-regional failure postoperative radio-chemotherapy (RT-CHT) is indicated. MATERIAL AND METHODS: Between 2004 and 2010, 182 patients with pathological stage II-III RC (TME performed - 41%, resection R0 - 88%, circumferential resection margin evaluated - 55.5% and was above 2 mm in 66% of them) received postoperative RT-CHT in our institution. Overall survival (OS) and LRFS were estimated with the Kaplan-Meier method. Univariate and multivariate analysis were performed to compare the impact of prognostic factors on survival. RESULTS: Five-year OS and LRFS rates were 63% and 85%, respectively. Loco-regional recurrence and isolated distant metastases rates were 11.5% and 19%, respectively. Multivariate analysis showed stage (III vs. II), HR: 2.3 (95% confidence interval [CI]: 1.4-3.8), p = 0.0001; extent of resection (R1-2 vs. R0), HR: 2.14 (95%CI: 1.14-3.99), p = 0.017, and age (>65 vs. ≤65 years), HR: 1.66 (95%CI: 1.06-2.61), p = 0.027 as prognostic factors for OS. Extent of resection (R1-2 vs. R0), HR: 3.65 (95%CI: 1.41-9.43), p = 0.008 had significant impact on LRFS. CONCLUSION: Despite a suboptimal quality of surgery and pathological reports, the outcome in our series is close to that reported in the literature. We confirm a strong impact of the extent of resection on patient's outcome, which confirms the pivotal role of surgery in the management of RC.

Accelerated hypofractionated radiotherapy with concurrent full dose chemotherapy for locally advanced non-small cell lung cancer: A phase I/II study.

INTRODUCTION: We report the results of toxicity and survival in stage III NSCLC patients treated with concurrent accelerated hypofractionated AHRT-CHT within a prospective study. METHODS: 92 patients received 3D-CRT or IMRT-planned RT: 58.8 Gy /21 fractions (2.8 Gy/fraction, 4 weeks) with 2 cycles of CHT (Cisplatin 80 mg/m2 D1 and D22; and Vinorelbine 25 mg/m2, D1, D8, D22, and D29) started with D1 of RT. Non-hematological toxicity was evaluated using RTOG-EORTC criteria, every week during treatment, one month after treatment completion, and every three months thereafter. RESULTS: Two patients did not receive the prescribed RT dose; 22 (24%) received only one CHT cycle. Median follow-up was 21.5 months (range: 1-65) for all patients and 32 months (range: 8-65) for living patients. There were: 13 (14%) cases of grade ≥III acute esophageal toxicity; 3 grade III acute pneumonitis, and 2 grade III late pulmonary toxicities. Two toxic deaths occurred within 3 months after treatment: fatal hemoptysis (1) and complications of esophageal toxicity (1). Five other deaths that occurred within one year after treatment were probably treatment-related: lung abscess (1), fatal hemoptysis (2), death from undetermined cause (2). Median overall survival was 38 months (95%CI:27-49), median progression free survival was 25 months (95%CI:14-36). CONCLUSIONS: Survival rates are encouraging, but the observed rate of toxic and probably toxic deaths is of potential concern. We proceed with the use of AHRT with concomitant full dose CHT, but patients with large PTV and major vascular abutment are excluded due to potentially increased risk of toxic death.

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study.

AIM: To evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation. BACKGROUND: Using oxaliplatin in the above setting is uncertain. PATIENTS AND METHODS: A subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group). RESULTS: Grade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39-1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83-6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52-1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43-1.40; p = 0.41), respectively. CONCLUSION: Our findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.

The risk of distant metastases in rectal cancer managed by a watch-and-wait strategy - A systematic review and meta-analysis.

BACKGROUND: The watch-and-wait (w&w) strategy is associated with frequent local regrowth (LR). Distant metastases (DM) occur more often in the patients with LR than in those without. However, it is unknown whether omitting immediate surgery results in the additional risk of DM. MATERIALS/METHODS: A systematic review and meta-analysis were performed to determine the maximum risk of additional DM. To estimate this, we used data showing the proportions of DM in patients with and without LR, assuming that the excess DM in patients with LR may develop in two ways: from subclinical DM already present at baseline and due to seeding from the uncontrolled primary tumor, and that the incidence of subclinical DM at baseline in the LR subgroup is at least not lower than in the non-LR subgroup. Based on the calculated rate of excess DM in the LR subgroup we have obtained the rate for the whole group of patients undergoing w&w. RESULTS: The maximum estimated risk of additional DM was 3.0% (95% CI: 1.2-4.9%) in the total group. After correction for short follow-up, the maximum risk at 5 years was 6.5%. Thus, the risk of excess DM is between 0% and 6.5%. Other evidence from a systematic review and the conservative assumptions taken for the calculation of the correction suggest that this maximum risk may be overestimated. CONCLUSIONS: The additional risk of DM seems to be low. However, the high probability of bias, heterogeneity of the patients' population and low quality of evidence make our estimation uncertain.