Decision Aids for Decision Making about Locally Advance Breast Cancer: A Systematic Review.

Locally advanced breast cancer (LABC) is a subset of breast cancer with locoregional progression without distant metastasis. The multimodality treatment (surgery, chemotherapy, radiotherapy, hormonal and targeted therapy if required) could significantly improve results in this specific group of patients. The complex and multiple options of treatment with similar mortality rates but different outcomes depending on the patient's desires, preferences and social environment require aid to facilitate the individual patient's decisions (e.g. Decision Aids (DAs) targeting patients considering primary or adjuvant treatment in LABC). In this context, DAs have been proven fundamental to help patients and clinicians share and agree on the best value option. The current systematic review aimed to evaluate the existing DAs related to these patients with LABC and identify current status and possible improvement areas (possible scarcity and heterogeneity of instruments, the status of their development, explanation of their purpose,…). No previous systematic reviews have been published on this topic. Following Prospero registration no: CRD42021286173, studies about LABC DAs were identified, without data or language restrictions, through a systematic search of bibliographic databases in December 2021. Quality was assessed using Qualsyst criteria (range 0.0-1.0). The quality of the 17 selected studies ranged from 0.46 to 0.95. Of them, 14/17 (82%) were DAs about treatment, only one (6%) about diagnosis, and 2/17 (12%) about the employment of DAs. No screening or follow-up DAs were retrieved. Twelve (70.6%) DAs were online tools. They varied broadly regarding their characteristics and purposes. Most of the studies focused on developing and testing different DAs (5/17; 29.4%) and their impact (7/17; 41.2%). Only 4/17 (23.5%) analysed their implementation and cost. These instruments have proven to improve patient's knowledge and decision-making, decrease patient anxiety, and patients tend to undergo treatment. However, nowadays, there is still a need for further research and consensus on methodology to develop practical DAs.

Short-term results of a phase II study of preoperative docetaxel/cisplatin/S-1 therapy for locally advanced gastric cancer.

BACKGROUND: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer. METHODS: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%. RESULTS: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively. CONCLUSIONS: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.

Astonishing Evolution in Oropharyngeal Cancer with Immunotherapy: A Case Report.

Background: Head and neck cancer is particular due to its infiltrative nature and lymphatic extension, with multidisciplinary treatment. Immunotherapy may be a brand-new therapeutic approach.Case Presentation: We report a case of patient with advanced head and neck cancer resistant to cytotoxic treatment, with astonishing response to antibodies anti Programmed Death 1 (PD1).Conclusion: Further studies are needed in order to obtained predictive index of immunotherapy responding, aiming to select appropriately patients for this treatment.

Laryngeal Preservation Rate and Salvage Therapy Following Initial Recurrence in a Real-world Setting After Definitive Radiation Therapy in Patients With Locally Advanced Laryngeal Squamous Cell Carcinoma.

Background/Aim: The larynx plays a pivotal role in vocalization and airway protection, and laryngeal cancer manifests through various symptoms. Contemporary strategies focus on laryngeal preservation, particularly through non-surgical modality therapies that utilize radiotherapy. The aim of this study was to assess the laryngeal preservation rate after definitive radiation therapy in patients with locally advanced laryngeal squamous cell carcinoma and investigate salvage therapy subsequent to the initial recurrence in a real-world context. Patients and Methods: Analysis included a total of 40 patients with locally advanced laryngeal squamous cell carcinoma who were treated with definitive radiotherapy in the University of Tokyo Hospital. Treatment involved external beam radiotherapy (70 Gy in 35 fractions) with elective nodal irradiation. The main study outcomes were assessment of survival, overall survival, local control, and the factors influencing laryngeal preservation. Results: The patients exhibited a median age of 64.5 years, and 80% of them were men. Chemotherapy was administered to 82.5% of the patients. The 3-year overall survival, progression-free, and laryngeal preservation survival rates were 86.3%, 66.8%, and 78.4%, respectively. Univariate and multivariate analyses identified chemotherapy to be significantly associated with favorable laryngeal preservation survival (p<0.001). Conclusion: Definitive radiotherapy results in favorable outcomes for laryngeal preservation in locally advanced laryngeal squamous cell carcinoma. This study emphasizes the importance of chemotherapy in comprehensive patient management. Nevertheless, larger prospective studies are crucial to validate and optimize therapeutic approaches for this condition.

Challenging case of deficient mismatch repair right-sided locally advanced adenocarcinoma of the ascending colon with duodenal involvement: A case report including step-by-step video of operation.

INTRODUCTION AND IMPORTANCE: Irresectable colon cancer presents a complex clinical challenge. Neoadjuvant immunotherapy has shown potential in improving resectability. Additionally, advancements in surgical techniques, including complete mesocolic excision (CME) with central vascular ligation (CVL), have contributed to better outcomes for right-sided colon cancer. This case report aims to demonstrate the successful laparoscopic resection of initial appearing irresectable colon cancer with suspected duodenal involvement. CASE PRESENTATION: A 70-year-old female presented with an irresectable mismatch repair deficient (dMMR) adenocarcinoma of the ascending colon with suspected duodenal ingrowth. Neoadjuvant treatment with pembrolizumab and ataluren resulted in a significant response, allowing for surgical resection. A laparoscopic right hemicolectomy with CME, including CVL, intracorporeal anastomosis and extraction through a Pfannenstiel incision, was performed. Additionally, the serosal layer of the duodenum was shaved after observing the absence of intraluminal invasion. Postoperatively, transient gastroparesis occurred, but overall outcomes were favourable. CLINICAL DISCUSSION: This case emphasizes the potential of immunotherapy in improving resectability for irresectable dMMR colon cancer with suspected involvement of surrounding organs. The combination of neoadjuvant therapy and advanced surgical techniques, such as CME with CVL, shows promise in achieving favourable clinical outcomes. However, further studies are needed to validate the effectiveness and safety of this combined approach in a larger cohort of patients. CONCLUSION: The successful laparoscopic resection of initially irresectable dMMR colon cancer with duodenal involvement, following neoadjuvant immunotherapy, demonstrated promising outcomes. This case advocates for further exploration of neoadjuvant treatments' efficacy, coupled with advanced surgical techniques, in managing locally advanced right-sided colon cancer.

The role of upfront neck dissection in definitive radiotherapy for locally advanced hypopharyngeal squamous cell carcinoma: A single-center retrospective analysis.

BACKGROUND: Hypopharyngeal cancer, constituting 3%-5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma. METHODS: This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate. RESULTS: This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control. CONCLUSION: This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials.

Upfront boost to gross disease followed by elective pelvic radiation improves compliance to radiation therapy delivery metrics in locally advanced vulvar cancer.

Locally advanced cancer of the vulva (LACV) is commonly diagnosed in older women (>65 years), and is treated using combined multimodality therapy (CMT) that includes radiation therapy (RT). Compliance to optimal RT metrics, including completion of > 20 fractions, overall treatment duration of < 8 weeks (56 days), and < 1 week intra-treatment break is associated with better disease outcomes. However, published results note that a significant number of patients with LACV do not adhere to these metrics. The aim of our study is to evaluate whether a modified sequence of RT delivery, treating the localized boost volume upfront followed by the larger elective nodal volume is associated with improved compliance to optimal RT delivery metrics.

Nontunneling Full Thickness Techniques for Neoplasia.

Colorectal cancer is the third most common cancer worldwide and the fourth leading cause of cancer-related deaths in the world, second in the United States. Although most lesions are managed surgically especially when they have already invaded into the submucosal layer, endoscopic full-thickness resection (EFTR) has become an emerging technique that can serve as a safe and effective alternative management for locally invasive gastrointestinal cancers. This article discusses the indications and various techniques and limitations of nontunneled EFTRs of gastrointestinal cancer and reviews the current literature on the outcomes of EFTR.

Prognostic risk factors for pT4 colon cancer: A retrospective cohort study.

The present study aimed to clarify the prognostic risk factors for pathological T4 (pT4) colon cancer and provide a basis for improved treatment in affected patients. The current retrospective cohort study included 83 consecutively enrolled patients who underwent curative surgery for primary pT4 colon cancer between January 2014 and December 2021 at Tokyo Medical Women's University (Tokyo, Japan). Oncological outcomes, including recurrence pattern, were compared between patients with pT4a and pT4b colon cancer. Independent risk factors associated with overall survival (OS) and relapse-free survival (RFS) were analyzed using a multivariate Cox regression model. The 3-year OS rates were 85.1 and 95.0% in the pT4a and pT4b groups (P=0.089) and 3-year RFS rates were 64.1 and 60.5% (P=0.589), respectively. Moreover, the 3-year peritoneal recurrence-free survival was 71.0 and 90.2% (P=0.085) in these groups, respectively. Independent risk factors for OS were histology (mucinous or poorly differentiated adenocarcinoma), tumor location (right-sided) and pN status (positive). The risk factors for RFS were histology and pN status. Patients with pT4b colon cancer and R0 resection may not have a poorer prognosis compared with those with pT4a colon cancer. However, patients with pT4a colon cancer tended to have more peritoneal recurrence patterns. Histology and pN status were associated with OS and RFS, and right-sided colon cancer was also a risk factor for OS.

New Scale Predicting Distant Recurrence in Locally Advanced Lower Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

BACKGROUND/AIM: Neoadjuvant chemoradiotherapy (nCRT) for locally advanced lower rectal cancer (LALRC) is effective in preventing locoregional recurrence; however, it is less effective for preventing distant recurrence. This study aimed to evaluate a new scale for predicting distant recurrence before administering nCRT. PATIENTS AND METHODS: Sixty-three patients underwent nCRT for LALRC between 2009 and 2016 at the Tokyo Women's Medical University. Of these, 51 consecutive patients who underwent curative surgery were enrolled in this study. Patients with ≥cT3 status or cN-positive LALRC were classified into three groups before nCRT based on the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR): high-risk, NLR ≥3.2 and LMR <5.0; intermediate-risk, NLR <3.2 and LMR ≥5.0 or NLR ≥3.2 and LMR <5.0; and low-risk, NLR <3.2 and LMR ≥5.0. Independent risk factors associated with distant relapse-free survival were analysed using the Cox proportional hazards model. Relapse-free survival from distant metastasis was evaluated using the log-rank test. RESULTS: Patient characteristics and tumour-associated factors were not significantly different between the groups. Distant recurrence in the high-, intermediate-, and low-risk groups was 61.5%, 42.9%, and 20.8% (p=0.046), respectively. In the multivariate analysis, the new scale was an independent risk factor for distant relapse-free survival (high-risk vs. low-risk groups, p=0.004 and intermediate-risk vs. low-risk groups, p=0.055). The 3-year distant relapse-free survival rate in the high-, intermediate-, and low-risk groups was 38.5%, 56.3%, and 81.7% (p=0.028), respectively. CONCLUSION: A new scale combining the pre-nCRT NLR and LMR was independently associated with distant relapse-free survival. The new scale for LALRC may aid selection for total neoadjuvant chemotherapy.

Clinicopathological features and survival outcomes for gastric adenocarcinoma: Real-world single-center data.

INTRODUCTION: Gastric cancer is the fifth most-common cancer and fourth common cause for cancer-related deaths globally. Surgery preceded or followed by chemotherapy or chemoradiotherapy is considered an optimal treatment for locally advanced gastric cancer. This study is a real-world data from a tertiary referral institute in southern India, in its experience with treating gastric adenocarcinoma over a period of four years with a minimum of two-year follow-up. METHODS: This was a retrospective analysis of data of patients with histologically proven gastric adenocarcinoma enrolled in the Department of Medical Oncology from 2015 to 2018. The demographic details, presentation, staging, treatment received and outcomes of patients with gastric adenocarcinoma were collected and analyzed in this study. RESULTS: Total 488 patients with gastric adenocarcinoma were included for the study. The stage-wise distribution of patients revealed early and locally advanced (45%) and metastatic (55%). The peritoneum and liver were the common sites of metastasis. The treatment distribution of these patients included perioperative chemotherapy followed by surgery (25 [5%]), surgery followed by adjuvant chemotherapy (65 [13%]), surgery alone (16 [3%]), perioperative chemotherapy alone (23 [4%]), palliative chemotherapy (274 [56%]) and supportive care (85 [17%]). The median overall survival for curative, palliative and supportive treatment was 23 (18-28), nine (7.6-10.4) and four (2.7-5.3) months, respectively. The two-year overall survival in the intention to treat population in the primary surgery (n = 81) and perioperative chemotherapy groups (n = 66) was 67.4% vs. 29.9% (p < 0.0001), respectively. CONCLUSION: This study highlights the advanced nature of the presentation of gastric cancer patients and the poor rate of treatment completion. The median survival rates in curative patients remain to be dismally poor. The treatment sequence in curable gastric cancer of surgery followed by adjuvant chemotherapy vs. perioperative chemotherapy followed by surgery needs to be explored in our country.

In Vivo Models for Studying Interstitial Photodynamic Therapy of Locally Advanced Cancer.

Interstitial photodynamic therapy (I-PDT) is a promising therapy considered for patients with locally advanced cancer. In I-PDT, laser fibers are inserted into the tumor for effective illumination and activation of the photosensitizer in a large tumor. The intratumoral light irradiance and fluence are critical parameters that affect the response to I-PDT. In vivo animal models are required to conduct light dose studies, to define optimal irradiance and fluence for I-PDT. Here we describe two animal models with locally advanced tumors that can be used to evaluate the response to I-PDT. One model is the C3H mouse bearing large subcutaneous SCCVII carcinoma (400-600 mm3). Using this murine model, multiple light regimens with one or two optical fibers with cylindrical diffuser ends (cylindrical diffuser fiber, CDF) can be used to study tumor response to I-PDT. However, tissue heating may occur when 630 nm therapeutic light is delivered through CDF at an intensity ≥60 mW/cm and energy ≥100 J/cm. These thermal effects can impact tumor response while treating locally advanced mice tumors. Magnetic resonance imaging and thermometry can be used to study these thermal effects. A larger animal model, New Zealand White rabbit with VX2 carcinoma (~5000 mm3) implanted in either the sternomastoid (neck implantation model) or the biceps femoris muscle (thigh implantation model), can be used to study I-PDT with image-based pretreatment planning using computed tomography. In the VX2 model, the light delivery can include the use of multiple laser fibers to test light dosimetry and delivery that are relevant for clinical use of I-PDT.

Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study.

INTRODUCTION: Since the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. RESULTS: In total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%-6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, -4.1%-5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5-56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8-68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. DISCUSSION: In practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated.

Combined Treatment with Laser Ablation and Tyrosine-Kinase Inhibitor as A Novel Multimodality Approach to Locally Advanced Thyroid Cancer: A Case Report.

BACKGROUND: Direct locoregional treatments were recently proposed for the local control of cervical and distant metastasis of thyroid cancer, but data on their use as part of a multimodality approach for primary thyroid tumors are poor. In this feasibility study, laser ablation (LTA) was successfully used for the initial debulking of unresectable radioiodine-refractory thyroid cancer in sequential therapy with Tyrosine-Kinase Inhibitors (TKI). CASE PRESENTATION: A 69-year-old woman underwent partial resection of papillary thyroid cancer with extensive tracheal infiltration. Post-treatment whole-body scan (131I, 8140 MBq) showed the absence of cervical thyroid uptake. The patient experienced a rapid increase in her cervical mass associated with dysphonia, dyspnea, and dysphagia. Due to a concomitant severe hypertensive state and cardiac failure, the patient was treated with LTA after a multidisciplinary consultation. After local anesthesia, two 300 nm optic fibers were inserted into the lesion through 21G spinal needles. Two illuminations with 4-watt output power and 3600 Joules energy delivery were performed with a diode-laser source. LTA resulted in rapid cancer debulking, and mass volume decreased from 23.9 to 7.5 mL resulting in significant improvement of pressure symptoms. Three months later, the patient was started on lenvatinib due to the initial regrowth of the tumor mass. The cervical tumor burden was controlled by TKI for 20 months when a rapid disease progression occurred, and the patient died. DISCUSSION: Locally advanced, unresectable, and radioiodine-refractory thyroid tumors can be managed with a novel multimodality approach. The initial debulking with LTA of the locally aggressive disease results in rapid control of the tumor burden threatening patients' life and is effectively followed by long-term control with TKI treatment. CONCLUSION: Based on this experience, sequential multimodality treatment with an initial locally directed laser ablation procedure followed by TKI therapy may be considered as a salvage option in patients with unresectable and rapidly progressive RR thyroid tumors.

Role of radio-ablative technique for optimizing the survival of patients with locally advanced pancreatic adenocarcinoma (Review).

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common and frequently diagnosed malignant tumor of the pancreas with few treatment options and poor life expectancy. Despite the advances in the surgical field, 40% of the patients are diagnosed with locally advanced disease which is not suitable for surgery. Radio-frequency ablation (RFA) has been described as a new 'weapon' in the multimodal treatment of PDAC, representing a cytoreductive procedure which must be completed with radiotherapy or chemo-radiotherapy. A systematic research was carried out utilizing the PubMed database in regards to this subject, to evaluate the role of RFA in PDAC management. Abstracts, letters-to-the-editor and non-English language manuscripts were excluded. The literature showed that RFA can be used in open and laparoscopic surgery but it is also feasible for endoscopic ultrasound (EUS-guided RFA) or percutaneous approach. Even though we found optimistic and encouraging reports on overall survival (OS), randomized studies are still required to corroborate these findings. Our review research underline that surgical resection remains the only radical treatment option, RFA being a safe and feasible technique reserved for unresectable, non-metastatic pancreatic tumors. Its combination with oncological treatment can improve the OS of these patients.

[Resection strategy for locally advanced thyroid carcinoma]. / Resektionsstrategien beim lokal fortgeschrittenen Schilddrüsenkarzinom.

Advanced thyroid carcinomas with infiltration of the aerodigestive tract are rare but are responsible for approximately 50% of the tumor-specific mortality. Due to impending and frequently life-threatening local complications and in the absence of promising therapeutic alternatives, a resection in curative or palliative intention is indicated if the local tumor is resectable. The resection and especially reconstruction of the trachea represent an extraordinary surgical challenge, require an individualized approach as well as exact knowledge of tracheal resection techniques. The decision for surgery in general, the selection of adequate resection and reconstruction strategies as well as the perioperative management should be accompanied by a particularly experienced interdisciplinary team.

Comparative Study of Neoadjuvant Chemotherapy Followed by Definitive Chemoradiotherapy Versus Definitive Chemoradiotherapy Alone in Locally Advanced Carcinoma of Cervix.

BACKGROUND: Carcinoma in the cervix is the most common malignancy and the fourth most common cause of death in females worldwide. It is the most common malignancy in India, the increasing incidence of cancer is escalating burden over radiation. This is a prospective randomized study comparing NACT followed by definitive chemoradiation versus chemoradiation. MATERIALS AND METHODS: This prospective randomized study analyzed 80 cervical cancer patients who were treated at our center during March 2017 and July 2018. Patients were divided into two arms: one received NACT and definitive CT/T and the other received definitive CT/RT. Statistical analysis was done using SPSS V.20 software. RESULTS: Overall response rate in our study was found to be 96.2%. In the study group, it was 97.5%, whereas in the control group, it was 95%. Majority of patients were in the age group 41-50 years, mainly stage IIb and IIIb. Tumor response in both the arms was similar and statistically significant (Chi2 = 0.348; p > 0.05). The hematologic toxicities ( p > 0.05) were more in the NACT group than in the CCRT group, while gastrointestinal toxicities were slightly higher in the control (statistically insignificant). CONCLUSION: NACT with taxane/platin followed by definitive CT/RT is as effective as the standard care in the treatment of locally advanced cervical cancer. It has even shown better results (p value > .005) and is also helpful in reducing systemic micrometastasis and bulk of the disease. It can be used as an alternative to the standard care at the places of long waiting time for the definitive treatment, without compromising the outcome.

Neoadjuvant Treatment of Stage IIB/III Triple Negative Breast Cancer with Cyclophosphamide, Doxorubicin, and Cisplatin (CAP Regimen): A Single Arm, Single Center Phase II Study (GBECAM 2008/02).

BACKGROUND: The DNA damaging platinum salts have been explored in the treatment of triple negative breast cancer (TNBC) based on preclinical, and, more recently, clinical evidence of specific susceptibility of TNBC to these agents. Despite the increased toxicity, treatment intensification with polychemotherapy improves response and might be of interest in patients presenting with large primaries. In this trial, we aimed at exploring the efficacy and tolerability of the addition of cisplatin to standard anthracycline-cyclophosphamide backbone in patients with stage IIB/III TNBC. PATIENTS AND METHODS: This is a single arm, single center, non-randomized, phase II trial of stage IIB/III TNBC. Patients received neoadjuvant chemotherapy with cisplatin (50 mg/m2) in combination with doxorubicin (50 mg/m2) and cyclophosphamide (500 mg/m2) every 21 days and for a total of six cycles (CAP). After surgery, adjuvant chemotherapy consisting of docetaxel (75 mg/m2) every 21 days was further provided for four cycles. Primary outcome was pathological complete response in the breast and axilla (pCR; ypT0ypN0). Secondary outcomes were safety, disease-free survival (DFS), and overall survival (OS). RESULTS: Eight (19.5%) out of 41 patients reached a pCR and 35 (85.4%) had a clinical complete or partial response. After a median follow-up of 47.4 months (interquartile range 30.9-61.9), the proportion of patients free of recurrence or death at 3 years was of 51.8% [95% confidence interval (CI) 34.6-66.5%], while the proportion of patients alive at 3 years was of 55.5% (95% CI 37.8-70.1%). Patients with a pCR rate or family history of breast and/or ovarian cancer showed a numerical but statistically non-significant trend for improved DFS and OS. The majority of patients received six cycles of CAP (82.9%). The three most common grade ≥3 adverse events were nausea (16.3%), vomiting (14.0%), and neutropenia (9.3%). Febrile neutropenia occurred in three patients (7.0%). CONCLUSION: Cisplatin in association with doxorubicin and cyclophosphamide was associated with a pCR rate of 19.5% in a cohort of patients with predominantly stage III tumors. The tolerability profile of this combination poses clinical challenges to its general use in clinical practice. UNIQUE IDENTIFIER NUMBER: GBECAM 2008/02. NCT IDENTIFIER NUMBER: NCT03304756.

Pretreatment serum lactate dehydrogenase is an independent prognostic factor for patients receiving neoadjuvant chemotherapy for locally advanced cervical cancer.

For locally advanced cervical cancer (LACC), hypoxia is a characteristic property. This study aimed to investigate whether baseline lactic dehydrogenase (LDH) level, which is a marker of hypoxia, had clinical value in determining neoadjuvant chemotherapy (NACT) response and prognosis for LACC patients. The study cohort included 418 patients with a median follow-up of 37.5 months. Cox proportional hazards models were used to assess the prognostic value of baseline LDH levels. Multivariate logistic regression analysis was performed to identify independent predictors of complete response after NACT. Backward stepwise selection with the Akaike information criterion was used to identify factors that could be entered into the multivariate regression model. Compared with patients with LDH levels <252.0 µ/L, patients with LDH levels ≥252.0 µ/L were more likely to have an elevated level of squamous cell carcinoma antigen, lymphatic vascular space involvement, lymph node metastasis, and positive parametrium and achieved lower complete remission rates. Baseline LDH levels ≥252.0 µ/L was an independent prognosticator for recurrence-free survival (adjusted hazard ratio [HR], 3.56; 95% confidence interval [CI] 2.22-5.69; P < 0.0001) and cancer-specific survival (adjusted HR, 3.08; 95% CI, 1.89-5.01; P < 0.0001). The predictive value of baseline LDH value remained significant in the subgroup analysis. LDH level ≥252.0 µ/L was identified as an independent predictor of complete remission after NACT (adjusted odds ratio [OR], 0.29; 95% CI, 0.15-0.58; P < 0.0001). Baseline LDH ≥252.0 µ/L is an independent prognostic predictor for patients receiving neoadjuvant chemotherapy for LACC. It helps distinguish patients with different prognosis and select patients who are more likely to benefit from NACT.

Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy.

BACKGROUND: Worldwide, almost one million new cases of stomach cancer were diagnosed in 2012, making it the fifth most common cancer, and the third leading cause of cancer deaths. The current tumor node metastasis (TNM) staging system represents a consensus between the East and the West, and will serve as a strong foundation upon which to build future evidence. In this review article, we first discuss the definition and optimal surgery for locally advanced gastric cancer, followed by the general principles when considering a pre vs. postoperative radiotherapy (RT) strategy. We then provide a synthesis of the existing randomized trial evidence in an attempt clarify the role of pre and postoperative RT in the management of locally advanced gastric cancer. METHODS: A Medline search 1966-Jun 2014 was undertaken. Randomized trials including patients with locally advanced gastric cancer (using established definitions), comparing RT [with or without chemotherapy (CT)], with surgery alone or other treatment modalities were included. Systematic reviews and evidence based practice guidelines that include this body of primary studies were preferentially discussed. Medline, Cochrane Library, Clinicaltrial.gov, Guidelines Clearinghouse were searched. RESULTS: Sixteen randomized trials, three systematic reviews and one practice guideline were included as the evidence base. In this group of studies, two reports compared postoperative chemoradiotherapy (CRT) with surgery alone. Driven predominantly by INT0116, they established the role of postoperative CRT to provide a survival benefit in a patient group that underwent surgery with predominantly D0-1 dissections. Preoperative RT (four studies) showed promise for survival benefit but the risks of bias in these trials were high. Postoperative CRT compared with CT alone (eight trials) showed no survival benefit with the addition of radiation although some evidence of activity can be observed with improved local regional control. CONCLUSIONS AND FUTURE DIRECTIONS: Technical expertise to enable the delivery of high quality RT to complex target volumes as is required in gastric cancer, and surgical standards to ensure the delivery of high quality surgery, have matured in recent years. Six trials with large sample sizes are currently ongoing to better define the role of preoperative CRT (two studies) and postoperative CRT (four studies), when used in conjunction with high quality surgery and RT, and contemporary CT regimens. The moderate likelihood of locoregional recurrences and the favorable therapeutic ratio with using RT preoperatively in other settings, provide optimism that preoperative CRT would have a pivotal role to play in locally advanced gastric cancer. Active accrual into ongoing trials is strongly encouraged.