Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

Current challenges in the treatment of gliomas:The molecular era

Gliomas originate from glial cells in the central nervous system.Approximately 80%-85%of malignant brain tumors in adults are gliomas.The most common central nervous system tumor in children is low-grade pediatric glioma.Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis.Molecular characterization has led to better diagnostic and prognostic staging,which in turn has increased the precision of treatment.Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma.However,improvements in survival have been modest.Currently,clinical guidelines,as well as the article by Mohamed et al accompanying this editorial piece,are adapting treatment recommendations(surgery,chemotherapy,and radiotherapy)according to diagnosis and prognosis guided by molecular biomarkers.Furthermore,this paves the way for the design of clinical trials with new therapies,which is especially important in pediatric gliomas.

Neoadjuvant treatment of rectal cancer: Where we are and where we are going

Locally advanced rectal cancer requires a multidisciplinary approach based on total neoadjuvant treatment with radiotherapy(RT)and chemotherapy(ChT),followed by deferred surgery.Currently,alternatives to the standard total neoadjuvant therapy(TNT)are being explored,such as new ChT regimens or the introduction of immunotherapy.With standard TNT,up to a third of patients may achieve a complete pathological response(CPR),potentially avoiding surgery.However,as of now,we lack predictive markers of response that would allow us to define criteria for a conservative organ strategy.The presence of muta-tions,genes,or new imaging tests is helping to define these criteria.An example of this is the diffusion coefficient in the diffusion-weighted sequence of magnetic resonance imaging and the integration of this imaging technique into RT treatment.This allows for the monitoring of the evolution of this coefficient over successive RT sessions,helping to determine which patients will achieve CPR or those who may require intensification of neoadjuvant therapy.

Circulating tumor cells in pancreatic cancer:The prognostic impact in surgical patients

Pancreatic cancer is associated with a poor prognosis,even in the early stages,mainly due to metastatic progression.New diagnostic techniques that predict unfavorable outcomes are needed in order to improve treatment strategies.Circulating tumor cells(CTCs)are showing promising results as a predictive biomarker for various tumors.In this editorial we comment on the article by Zhang et al,who published the first systematic review and meta-analysis evaluating the prognostic value of CTCs as biomarkers in early-stage pancreatic cancer patients undergoing surgery.CTCs were detected in peripheral or central venous system blood,before or during surgery.Positive CTCs showed a correlation with decreased overall survival and decreased relapse-free,disease-free and progression-free survival in this meta-analysis.However,the heterogeneity was significant.The authors suggest that this result was related to the separation methods used between studies,but other differences such as the margin status or the neoadjuvant and adjuvant treatments used are also important to consider.CTCs may be a potential prognostic biomarker in pancreatic cancer patients,but it is necessary to compare and standardize the platforms used to isolate CTCs,to compare different biomarkers from liquid biopsy and to determine the impact on prognosis when therapeutic changes are made based on CTCs levels.

Pembrolizumab autoimmune related diabetes:Moving forward,keep learning

Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged survival.The side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most frequent.Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of life.The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.

Hyoid metastasis an unusual location from lung cancer

Bone metastases from lung cancer account for 8.5%,with those located in the hyoid bone being extremely rare.In this editorial,we made a review about Hsu et al case report highlighted the importance of palliative radiotherapy,even with an unusual but effective scheme in pain control in a patient with non-small cell lung cancer in stage IV.

Current status of anaplastic thyroid carcinoma

In this editorial we comment on the article by Pavlidis et al,published in the recent issue of the World Journal of Oncology.We focus on the recent contributions in the management of anaplastic thyroid carcinoma,highlighting the importance of surgery and radiotherapy as first line therapies in its management and the introduction of new systemic therapies beyond chemotherapy,focused on molecular alterations,an essential step in the diagnosis and included in clinical guidelines for the selection of the ideal treatment.In contrast to other neoplasms,immunotherapy,is still beginning in studies of this pathology with encouraging results.Therefore,multimodal management of the pathology together with new drugs seems to be the logical step to increase the survival of this neoplasm.

Vitamin D and prostate cancer prevention

Vitamin D is a hot topic nowadays,especially its relationship with cancer pre-vention.Normally,vitamin D is associated with bone health principally,but the new research has discovered an impact on immune function and cellular sig-naling,even in same studies talk about a hormone,however,the most important relationship is its implication in cellular processes,inhibiting cancer growth.For now,the recent studies are oriented about a benefit and a cause-effect relationship between prostate cancer and normal levels of vitamin D.This premise opens a lot of questions in this scenario.This editorial highlighted the most important studies in this area.

Potential role of transmembrane 9 superfamily member 1 as a biomarker in urothelial cancer

Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel therapies.Many proteins involved in the molecular mechanisms are currently an enigma,especially the transmembrane 9 superfamily member 1 which has an unclear function.Wei et al published the function and mechanism of this protein,and showed that it could participate in the proliferation,migration and invasion of tumor cells in bladder cancer,therefore treatments directed against this protein may be beneficial in avoiding this condition.

Bridging the gap: Predicting brain metastasis in breast cancer

Chen et al explored clinicopathological features and prognostic factors,revealing advanced tumor stage,lung metastases,HER-2 overexpression,and triple-negative status as key contributors.Recent research connects astrocytes'role in brain metastasis with signaling pathways and the impact of Trastuzumab on HER-2 tumor survival.Factors such as positive HER2 status,lack of estrogen receptor expression,and liver metastasis are identified as additional risk factors.The routine use of magnetic resonance imaging,insights into gene mutations associated with metastasis,and the role of radiotherapy,including prophylaxis possibilities,is controversial in clinical practice.Understanding these risk factors in a multidisciplinary collaboration is precise for local treatments and targeted therapies,particularly for HER2+tumors,impacting directly on longer survival.

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, therehas been a growing interest in alternative approaches with less morbidity,including the organ-preserving watch and wait strategy, in which surgery isomitted in patients who have achieved a cCR. These patients are managed with aspecific follow-up protocol to ensure adequate cancer control, including the earlyidentification of recurrent disease. However, there are several open questionsabout this strategy, including patient selection, the clinical and radiologicalcriteria to accurately determine cCR, the duration of neoadjuvant treatment, therole of dose intensification (chemotherapy and/or radiotherapy), optimal followupprotocols, and the future perspectives of this approach. In the present review,we summarize the available evidence on the watch and wait strategy in thisclinical scenario, including ongoing clinical trials, QoL in these patients, and thecontroversies surrounding this treatment approach.

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.

New standard in locally advanced rectal cancer

In the following review we intend to ascertain the optimal neoadjuvant therapy inpatients with locally advanced rectal cancer. In 2004, a study revealed thatchemoradiotherapy (CRT) resulted in better local control when performedpreoperatively rather than postoperatively, thus neoadjuvant treatment wasestablished as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant differencebetween concomitant CRT over 5 wk vs short-course radiotherapy (RT).Therefore, both were established as standard neoadjuvant treatments. Later, theStockholm III study demonstrated that short-course RT had a higher completepathological response than long-course RT. It also showed that a delay betweenRT and surgery presented fewer complications. This opened a window of time toprovide an early and effective systemic treatment to prevent distant metastases.Studies show that short-course RT plus oxaliplatin-based chemotherapy couldachieve this. When comparing this total neoadjuvant treatment (TNT) vsconcomitant CRT, the former showed greater complete pathological response andlower acute toxicity. Studies presented during 2020 have also shown the benefitsof TNT in terms of complete pathological response, as well as disease andmetastasis-free survival. Our review suggests that probably TNT should be thenew standard treatment for these patients. However, we will have to wait for thefull text publications of these studies to confirm this statement.

Deep diving in the PACIFIC:Practical issues in stage III non-small cell lung cancer to avoid shipwreck

After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients.The 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of SCLC.These guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and radiotherapy.Finally,we discuss the main indications for reirradiation in local recurrence.

Stereotactic body radiation therapy:A good dance partner of oligometastatic non-small cell lung cancer to the sound of SINDAS study

The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both primary and metastatic)should be amenable to radical intent treatment with acceptable toxicity.Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes;however,due to the diverse selection criteria and treatment strategies used in those studies,it is difficult to compare directly results to draw definitive conclusions.In recent years,prospective phase II trials,such as the SABR-COMET and"Oligomez"trials,have shown that stereotactic body radiation therapy(SBRT)improves outcomes in patients with OMD.More recently,interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer.In the present editorial,we review the definition and historical context of advanced non-small cell lung cancer with OMD.In addition,we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies.We also discuss in depth the results of the SINDAS study,including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

Advances and controversies in the management of early stage nonsmall cell lung cancer

Complete resection continues to be the gold standard for the treatment of earlystage lung cancer.The landmark Lung Cancer Study Group trial in 1995 established lobectomy as the minimum intervention necessary for the management of early-stage non-small cell lung cancer,as it was associated with lower recurrence and metastasis rates than sublobar resection and lower postoperative morbidity and mortality than pneumonectomy.There is a growing tendency to perform sublobar resection in selected cases,as,depending on factors such as tumor size,histologic subtype,lymph node involvement,and resection margins,it can produce similar oncological results to lobectomy.Alternative treatments such as stereotactic body radiotherapy and radiofrequency ablation can also produce good outcomes in inoperable patients or patients who refuse 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.

Postoperative radiotherapy in resected non-small cell lung cancer:The never-ending story

This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung cancer.It also systematically reviews the current evidence,the international recommendations in the most relevant guidelines,the most controversial aspects in clinical and pathological staging,the specific technical aspects of radiotherapy treatment,and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients,evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical evolution.Finally,currently active trials that aspire to provide more evidence on this topic are reviewed.