A case report: Pathological complete response to neoadjuvant lorlatinib for Epithelioid inflammatory myofibroblastic sarcoma with EML4-ALK rearrangement.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor originating from mesenchymal tissue. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) represents a rare and particularly aggressive variant, associated with a worse prognosis. Almost all EIMS cases exhibits activating anaplastic lymphoma kinase (ALK) gene rearrangements, which suggests that EIMS patients may potentially benefit from treatment with ALK tyrosine kinase inhibitors (TKIs). We presented a case involving a 34-year-old woman who was diagnosed with mediastinal EIMS and had a rare echinoderm microtubule-associated protein-like 4 (EML4) -ALK fusion. Following 15 months of neoadjuvant lorlatinib treatment, the patient underwent a complete surgical resection, resulting in a pathological complete response. Given the heightened risk of postoperative recurrence associated with EIMS, the patient's treatment plan included ongoing adjuvant therapy with lorlatinib. As of the present moment, the patient has achieved an overall survival of over 2 years with no observed tumor recurrence. Consequently, the case offers valuable clinical evidence supporting the potential benefits of neoadjuvant lorlatinib treatment for ALK-positive locally mediastinal EIMS patients, with a demonstrated tolerable safety profile.

Exploring the Therapeutic Potential of Lenvatinib: A Complete Pathological Response in an Operable Case of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with increasing incidence and mortality rates. This case report presents a unique instance of a 66-year-old male patient with operable HCC who achieved a complete pathological response after short-term preoperative treatment with lenvatinib. The patient, with a history of diabetes and hypertension, was diagnosed with HCC and started on lenvatinib due to logistical reasons. Despite discontinuing the treatment after one week due to altered sensorium, a significant reduction in tumor size was observed. The patient underwent successful surgery, and the final histopathology report indicated a complete pathological response. This case highlights the potential of lenvatinib as a therapeutic option in the management of HCC, even in operable cases, and opens avenues for further research into its efficacy and applicability.

Immune Checkpoint Blockade in Melanoma - Earlier is Better?

Neoadjuvant immunotherapy is a promising approach for resectable stage III melanoma. It has shown higher response rates and improved tumor regression compared to adjuvant therapy alone. Neoadjuvant ICIs also demonstrate favorable survival outcomes. Recent trials, such as one with pembrolizumab, reported significantly improved event-free survival. Neoadjuvant ICIs offer advantages like T cell expansion, early-stage efficacy, treatment assessment through surgical specimens, and potential tumor size reduction for better surgical outcomes. However, further research is needed to optimize patient selection and treatment protocols.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma.

BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Effectiveness and safety of neoadjuvant therapy in triple-negative breast cancer in a real-world population. / [Artículo traducido] Efectividad y seguridad del tratamiento neoadyuvante del cáncer de mama triple negativo en la vida real.

OBJECTIVE: Triple-negative breast cancer is a subtype of aggressive breast cancer. Our aim is to evaluate the effectiveness and safety of neoadjuvant treatment in early-stage triple-negative breast cancer and to identify predictors of pathological complete response. METHODS: This is a single-center, retrospective study involving 79 patients with triple-negative breast cancer who initiated neoadjuvant treatment between January 2017 and October 2022. Descriptive analyses were performed as appropriate. Statistical analysis utilized bivariate logistic regression to explore the presence of factors related to pathological complete response, and the Kaplan-Meier method was employed for survival analysis. RESULTS: In the overall population, 27 patients (n = 78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n = 73; 42.5%) achieved a grade 5 pathological complete response in the breast, according to the Miller and Payne classification. The addition of platinum to standard therapy improved both breast and axillary lymph node pathological complete response rates. Age less than 40 years was identified as a predictor of pathological complete response in our study population through bivariate analysis, while Ki67 levels lower than 70% were associated with a lower pathological complete response rate. Adverse events were reported in 72 patients (91.1%), with grade 3-5 adverse events observed in 33 (41.8%). There was a particularly notable increase in gastrointestinal and hematological adverse events when platinum was added. CONCLUSIONS: In this population, we observed moderate rates of pathological complete response with acceptable chemotherapy tolerance. Platinum-based chemotherapy appears to enhance the likelihood of achieving pathological complete response, albeit with a less favorable safety profile. Therefore, evaluating the benefit-risk balance is crucial when selecting the optimal chemotherapy regimen for individual patients.

Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement.

PURPOSE: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. MATERIALS AND METHODS: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. RESULTS: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). CONCLUSION: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

Cost-effectiveness of Pembrolizumab in Combination with Chemotherapy as Neoadjuvant Treatment and Continued as a Single Agent Adjuvant Treatment for High-Risk Early-Stage Triple-Negative Breast Cancer in Hong Kong.

INTRODUCTION: The phase III randomized KEYNOTE-522 trial demonstrated that pembrolizumab in combination with chemotherapy as neoadjuvant treatment followed by adjuvant pembrolizumab (pembrolizumab + chemotherapy) provided significant improvements in event-free survival (EFS) and overall survival (OS) for patients with high-risk early-stage triple-negative breast cancer (eTNBC). The objective was to assess the cost-effectiveness of pembrolizumab + chemotherapy compared to neoadjuvant chemotherapy alone (chemotherapy) in patients with high-risk eTNBC from a Hong Kong third-party payer perspective. METHODS: A multistate transition model with four health states (event-free), locoregional recurrence, distant metastases, and death) was developed to assess the lifetime medical costs and health outcomes (3% annual discount), along with incremental cost-effectiveness ratios (ICERs) using efficacy and safety data from the KEYNOTE-522 trial. The health state utilities were derived from KEYNOTE-522 Euro-QoL-five-dimension five-level questionnaire (EQ-5D-5L) data. Costs were expressed in 2022 Hong Kong dollars (HKD). Scenario and sensitivity analyses were performed to assess the robustness of results. RESULTS: Over a 32-year time horizon, base case results showed that pembrolizumab + chemotherapy was associated with a 3.42 year longer EFS and expected gains of 3.05 life years (LYs) and 2.45 quality-adjusted life years (QALYs) compared to chemotherapy. The resultant ICERs were HKD 135,200 per QALY gained and HKD 108,463 per LY gained, which were lower than the World Health Organization (WHO) cost-effectiveness threshold of three times gross domestic product (GDP) per capita for Hong Kong of HKD 1,171,308 per QALY. The one-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) showed the results were robust across various inputs and alternative scenarios. CONCLUSION: On the basis of the analysis conducted for a 56-year-old cohort with high-risk eTNBC and assumptions in the model, pembrolizumab + chemotherapy represents a cost-effective proposition (as the ICER is approximately 35% of the GDP per capita in Hong Kong) for patients with high-risk eTNBC in Hong Kong.

The manuscript outlines the methods and results of a health economic model to estimate the cost-effectiveness of pembrolizumab + chemotherapy compared to neoadjuvant chemotherapy alone (chemotherapy) in patients with high-risk early-stage triple-negative breast cancer in the Hong Kong setting. The results of the manuscript show that the combination of pembrolizumab and chemotherapy provides an additional 3.05 life years and 2.45 quality-adjusted life years. Despite the potential drawbacks of employing gross domestic product (GDP) as a proxy for cost-effectiveness thresholds, the incremental cost-effectiveness ratio was less than three times GDP per capita in Hong Kong. Therefore, the new intervention was cost-effective. However, like any similar study, the results rely substantially on extrapolation of trial outcomes and thus sensitivity analysis has also been performed to handle the uncertainty associated with results. The one-way sensitivity analyses and probabilistic sensitivity analysis showed the results were robust. The manuscript provides economic evidence of the new intervention and provides new clinical insights.

Case report: Pathological complete response to neoadjuvant brigatinib in stage III non-small cell lung cancer with ALK rearrangement.

Purpose: The use of neoadjuvant anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) has not been extensively explored. The current case report highlights the notable pathological complete response (pCR) achieved following neoadjuvant brigatinib therapy in a patient with stage IIIA ALK-positive non-small cell lung cancer (NSCLC). Case presentation: A 32-year-old male presented with incidental lung lesions, ultimately diagnosed as clinical stage T3N1M0, IIIA NSCLC with an ALK gene rearrangement. Following a multidisciplinary discussion, the patient opted for neoadjuvant brigatinib therapy, which significantly reduced the tumor size. Subsequently, surgery with curative intent was performed, revealing pCR with no residual tumor cells. The patient remained disease-free during a 13-month follow-up period. Conclusion: This case report provides compelling evidence of pCR following brigatinib therapy in ALK-positive NSCLC, suggesting that surgery after neoadjuvant therapy with brigatinib may offer a safe and effective approach for patients with ALK-positive NSCLC.

Total mesorectal excision after rectal-sparing approach in locally advanced rectal cancer patients after neoadjuvant treatment: a high volume center experience.

Background: In patient with a complete or near-complete clinical response after neoadjuvant treatment for locally advanced rectal cancer, the organ-sparing approach [watch & wait (W&W) or local excision (LE)] is a possible alternative to major rectal resection. Although, in case of local recurrence or regrowth, after these treatments, a total mesorectal excision (TME) can be operated. Method: In this retrospective study, we selected 120 patients with locally advanced rectal cancer (LARC) who had a complete or near-complete clinical response after neoadjuvant treatment, from June 2011 to June 2021. Among them, 41 patients were managed by W&W approach, whereas 79 patients were managed by LE. Twenty-three patients underwent salvage TME for an unfavorable histology after LE (11 patients) or a local recurrence/regrowth (seven patients in LE group - five patients in W&W group), with a median follow-up of 42 months. Results: Following salvage TME, no patients died within 30 days; serious adverse events occurred in four patients; 8 (34.8%) patients had a definitive stoma; 8 (34.8%) patients undergone to major surgery for unfavorable histology after LE - a complete response was confirmed. Conclusion: Notably active surveillance after rectal sparing allows prompt identifying signs of regrowth or relapse leading to a radical TME. Rectal sparing is a possible strategy for LARC patients although an active surveillance is necessary.

The Role of Lymph Node Downstaging Following Neoadjuvant Treatment in a Group of Patients with Advanced Stage Cervical Cancer.

Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment-p: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention-p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage-p: 0.002 and on the lymph node status evaluated during surgical intervention-p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.

Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2-positive early breast cancer: real-world data from NeoPowER study.

BACKGROUND: The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population. METHODS: We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables. RESULTS: 260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009). CONCLUSIONS: Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.

Mapping of lymph node metastasis from esophageal squamous cell carcinoma after neoadjuvant treatment: a prospective analysis from a high-volume institution in China.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

Utilization and survival outcomes of neoadjuvant chemotherapy for early-stage gastric cancer.

BACKGROUND AND OBJECTIVES: Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers. METHODS: The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010-2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan-Meier methods and Cox regression assessed overall survival (OS). RESULTS: Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2-64.0) versus 45.6 months (IQR 22.5-72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05-1.34). CONCLUSIONS: Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes.

[Progress and Discussion of Perioperative Targeted Therapy in Patients 
with EGFR-mutated Resectable Non-small Cell Lung Cancer].

Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches.
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A prospective single-center, single-arm, open-label, phase II study of sintilimab and anlotinib combined with chemotherapy in neoadjuvant treatment of resectable esophageal cancer.

BACKGROUND: Antiangiogenic treatment and immunochemotherapy effectively treat patients with advanced esophageal cancer. However, there remains a dearth of studies concerning neoadjuvant therapy for resectable esophageal cancer. METHODS: The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for antiangiogenesis and sintilimab (200 mg) and chemotherapy for three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) and safety. RESULTS: Out of the 34 screened patients, 17 were successfully enrolled in the study, and 14 completed the entire treatment process. The pCR was 35.3% (6/17). However, two patients experienced mortality. The occurring rate of grade 3 or higher complications after the surgery was 78.6% (11/14) according to Clavien-Dindo classification. Specifically, anastomotic leakage was observed in 57.1% (8/14) of the patients. CONCLUSION: Compared to neoadjuvant chemotherapy, the current regimen demonstrated improved pCR. However, it did not show significant improvement compared to immunochemotherapy. It is essential to exercise caution when using this treatment approach in patients with esophageal cancer as it might increase postoperative complications, especially anastomotic leakage.

Effectiveness and safety of neoadjuvant therapy in triple-negative breast cancer in a real-world population.

OBJECTIVE: Triple-negative breast cancer is a subtype of aggressive breast cancer. Our aim is to evaluate the effectiveness and safety of neoadjuvant treatment in early-stage triple-negative breast cancer and to identify predictors of pathological complete response. METHODS: This is a single-center, retrospective study involving 79 patients with triple-negative breast cancer who initiated neoadjuvant treatment between January 2017 and October 2022. Descriptive analyses were performed as appropriate. Statistical analysis utilized bivariate logistic regression to explore the presence of factors related to pathological complete response, and the Kaplan-Meier method was employed for survival analysis. RESULTS: In the overall population, 27 patients (n=78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n=73; 42.5%) achieved a grade 5 pathological complete response in the breast, according to the Miller and Payne classification. The addition of platinum to standard therapy improved both breast and axillary lymph node pathological complete response rates. Age less than 40 years was identified as a predictor of pathological complete response in our study population through bivariate analysis, while Ki67 levels lower than 70% were associated with a lower pathological complete response rate. Adverse events were reported in 72 patients (91.1%), with grade 3-5 adverse events observed in 33 (41.8%). There was a particularly notable increase in gastrointestinal and hematological adverse events when platinum was added. CONCLUSIONS: In this population, we observed moderate rates of pathological complete response with acceptable chemotherapy tolerance. Platinum-based chemotherapy appears to enhance the likelihood of achieving pathological complete response, albeit with a less favorable safety profile. Therefore, evaluating the benefit-risk balance is crucial when selecting the optimal chemotherapy regimen for individual patients.

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, distant tumor recurrence remains a concern, prompting the exploration of total neoadjuvant therapy (TNT) as a comprehensive treatment strategy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Nonoperative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving complete clinical response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for the assessment of treatment response. This review synthesizes current evidence on TNT, ICIs, NOM, and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

Can the Pathological Response in Patients with Locally Advanced Gastric Cancer Receiving Neoadjuvant Treatment Be Predicted by the CEA/Albumin and CRP/Albumin Ratios?

Background: The purposes of neoadjuvant chemotherapy are to tumor size to improve the tumor removal rate, extend survival, and prevent metastasis. In this study, the importance of CRP/albumin ratio and CEA/albumin ratio in the prediction of neoadjuvant treatment response in gastric cancer patients was evaluated. Methods: This study retrospectively included 135 gastric cancer patients who received neoadjuvant chemotherapy at Çukurova University Balcali Hospital between January 2018 and December 2023. Preoperative CRP/albumin and CEA/albumin ratios were compared according to treatment response and multivariate logistic regression analysis was performed to determine the potential importance of these ratios in predicting pathological response. Results: The mean age of the 135 patients was 58.79 ± 10.83 (min = 26-max = 78). The CRP/albumin and CEA/albumin ratios were found to be significantly lower in patients who did not respond to neoadjuvant therapy. Each 1-unit increase in the CRP/albumin ratio was associated with a 1.16-fold decrease in the odds of pathological complete response to neoadjuvant therapy. Both CRP/albumin and CEA/albumin ratios were found to be significant in distinguishing neoadjuvant therapy response. The optimal cut-off value was 2.74 for the CRP/albumin ratio (sensitivity = 60%, specificity = 78.4%) and 1.40 for the CEA/albumin ratio (sensitivity = 74.2%, specificity = 67.6%). Values below these cut-off points favored neoadjuvant therapy response. Pathological complete response to neoadjuvant therapy was 4.75 times higher in patients with a CRP/albumin ratio below 2.74 and 5.14 times higher in patients with a CEA/albumin ratio below 1.40. Conclusions: Findings demonstrate that in patients with locally advanced gastric cancer receiving neoadjuvant treatment, CRP/Albumin and CEA/Albumin ratios are significant markers of pathological response.