Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors in Locally Advanced Rectal Cancer.

INTRODUCTION: The standard therapy for locally advanced rectal cancer (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study was to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathologic complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. METHODS: We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received nCRT based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT was obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's χ2 or Fisher's exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. RESULTS: Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68-83). All patients received radiotherapy up to 50.4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery, 38% had elevated basal NLR (cut-off >1.95), and 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55-88), a lower DFS was obtained in the high NLR subgroup (log-rank, Mantel-Cox 5.165, p = 0.023) and in the high PLR subgroup (log-rank, Mantel-Cox 13.971, p = 0.001). Multivariate analysis showed that PLR (p = 0.006) was a strong significant predictor of DFS. A lower OS was observed in the high NLR and PLR subgroup without significant differences (log-rank, Mantel-Cox 1.245, p = 0.265; 0.578, p = 0.447). No significant differences were obtained in any of the subgroup analysis regarding pCR rates. CONCLUSION: In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.

Current treatment landscape for oligometastatic non-small cell lung cancer.

The management of patients with advanced non-small cell lung carcinoma (NSCLC) has undergone major changes in recent years. On the one hand, improved sensitivity of diagnostic tests, both radiological and endoscopic, has altered the way patients are staged. On the other hand, the arrival of new drugs with antitumoral activity, such as targeted therapies or immunotherapy, has changed the prognosis of patients, improving disease control and prolonging survival. Finally, the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body. All of these advances have impacted the treatment of patients with advanced lung cancer, especially in a subgroup of these patients in which all of these treatment modalities converge. This poses a challenge for physicians who must decide upon the best treatment strategy for each patient, without solid evidence for one optimal mode of treatment in this patient population. The aim of this article is to review, from a practical and multidisciplinary perspective, published evidence on the management of oligometastatic NSCLC patients. We evaluate the different alternatives for radical ablative treatments, the role of primary tumor resection or radiation, the impact of systemic treatments, and the therapeutic sequence. In short, the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

Relationship between nutritional treatment compliance and nutritional status improvements in patients with gastrointestinal impairment taking an oral peptide-based supplement.

OBJECTIVES: Compliance in outpatients with gastrointestinal (GI) malabsorption is key in nutritional treatment. The objective of this study was to assess compliance in patients with GI impairment and malnutrition taking a high-calorie, high-protein, peptide-based oral nutritional supplement (ONS-PBD). METHODS: A prospective, multicenter, observational study was conducted in 19 medical sites in Spain where ONS-PBD were prescribed as standard of care. Patients consumed ONS-PBD daily for 12 wk. Compliance was calculated as the percentage consumed of the prescribed amount of ONS per day. RESULTS: A total of 90 adult patients were included in the study, of whom 64 completed the 12-wk regimine. Mean compliance was 78.8% ± 24.5%. Risk of malnutrition decreased in 56.3% of patients at 12 wk, as measured with the malnutrition universal screening tool. A reduction in abdominal pain was observed and stool consistency improved, with a mean of 54.7% and 27.5%, respectively. Improvements in quality of life and a decrease in percentage of patients with severe functional impairment were observed. CONCLUSIONS: These data show that ONS-PBD compliance in malnourished patients with GI symptoms is high, reducing GI symptoms and improving patients' nutritional status.

GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis and rising incidence. Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement. Numerous therapeutic advances have been made in recent years, including the use of less aggressive surgical techniques associated with lower morbidity and mortality (e.g., pleurectomy/decortication), technological advancements in the field of radiotherapy (intensity-modulated radiotherapy, image-guided radiotherapy, stereotactic body radiotherapy, proton therapy), and developments in systemic therapies (chemotherapy and immunotherapy). These improvements have had as yet only a modest effect on local control and survival. Advances in the management of MPM and standardization of care are hampered by the evidence to date, limited by high heterogeneity among studies and small sample sizes. In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology, we review clinical, histologic, and therapeutic aspects of MPM, with a particular focus on all aspects relating to radiotherapy, including the current evidence base, associations with chemotherapy and surgery, treatment volumes and planning, technological advances, and reradiation.

Watch and wait approach in rectal cancer: Current controversies and future directions.

According to the main international clinical guidelines, the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. However, doubts have been raised about the appropriate definition of clinical complete response (cCR) after neoadjuvant therapy and the role of surgery in patients who achieve a cCR. Surgical resection is associated with significant morbidity and decreased quality of life (QoL), which is especially relevant given the favourable prognosis in this patient subset. Accordingly, there has been a growing interest in alternative approaches with less morbidity, including the organ-preserving watch and wait strategy, in which surgery is omitted in patients who have achieved a cCR. These patients are managed with a specific follow-up protocol to ensure adequate cancer control, including the early identification of recurrent disease. However, there are several open questions about this strategy, including patient selection, the clinical and radiological criteria to accurately determine cCR, the duration of neoadjuvant treatment, the role of dose intensification (chemotherapy and/or radiotherapy), optimal follow-up protocols, and the future perspectives of this approach. In the present review, we summarize the available evidence on the watch and wait strategy in this clinical scenario, including ongoing clinical trials, QoL in these patients, and the controversies surrounding this treatment approach.

Metformin and statins: a possible role in high-risk prostate cancer.

AIM AND BACKGROUND: There is increasing evidence that statins and oral anti-diabetic drugs, such as metformin, can have a favorable role in advanced prostate cancer treatment.Metformin has been shown to inhibit proliferation of tumor cells in vitro and statins inhibit carcinogenesis by suppressing angiogenesis/invasion mechanisms. However, clinical evidence on the protective effect of these drugs is still weak.The purpose of this study is to analyze if these drugs have an impact on Biochemical-Failure-Free-Survival (BFFS) and on Distant-Failure-Free-Survival (DFFS) in localized high-risk prostate cancer. MATERIAL AND METHODS: From 2002-2016, 447 patients with histologically confirmed high-risk prostate cancer were retrospectively evaluated. All patients received radiotherapy and androgen deprivation therapy. Biochemical recurrence was determined by the Phoenix criteria and metastatic patients were defined by the presence of radiological metastasis. Survival analysis was performed using the Kaplan-Meier method. RESULTS: 175 patients were treated with statins (65.3 % with a dose ≤ 20 mg/day) and 70 with metformin (75.7 % with a dose ≤ 1700 mg/day). Median follow-up was 88 months (1-194) with no differences in BFFS and DFFS between metformin and non-metformin patients (77.4 % versus 80 %, p = 0.91 and 89.4 % versus 88.7 %, p = 0.56, respectively). We did not find a statistical difference in BFFS and DFFS in patients taking higher doses of those drugs. CONCLUSION: Metformin and statins were not associated with BFFS or DFFS improvement in our analysis. However, the small number of patients treated with these drugs limits the reliability of the results and prospective studies are needed.

Neck dissection after radiochemotherapy in patients with locoregionally advanced head and neck cancer.

BACKGROUND: Primary chemoradiation is a frequent treatment for locoregionally advanced head and neck squamous cell carcinoma. Some authors claim that a neck dissection (ND) is necessary in N2/N3 disease after this treatment in order to avoid regional recurrences. The aim of this study was to determine the incidence of isolated nodal failure in patients with N2/N3 disease who achieved a complete clinical and radiological response (CR) after chemoradiation, when no planned ND was performed. METHODS: We retrospectively analysed the survival rates, nodal response and subsequent neck nodal control of 28 patients with locally advanced oropharynx, hypopharynx or larynx squamous cell carcinoma disease, treated with primary chemoradiation. RESULTS: With a median follow-up of 28 months, 2-year global survival was 73% and disease-free survival 60%. Patients who had complete local and regional response after chemoradiotherapy were followed, with 100% neck nodal control. CONCLUSION: Patients with N2/N3 disease who obtained a clinical and radiological CR to chemoradiation had a zero incidence of isolated neck failure without a planned ND. The continued use of planned NDs in this patient subset may not be justified. This can be further confirmed in randomised prospective trials.