Low-dose immunotherapy as a potentiator to increase the response with neo-adjuvant chemotherapy in oral cancers

Neo-adjuvant chemotherapy(NACT)is utilized in locally advanced oral cancers to reduce the tumor burden and downstage the tumor to be amenable for definitive surgical management.Its long-term results compared to upfront surgical resection was not encouraging.Immunotherapy has now been used not only in recurrence and metastatic setting but also in the locally advanced tumor management regimens.The purpose of this concept paper is to bring forward the rationale to use a fixed low-dose immunotherapy agent as a potentiator to the standard NACT regimen and recommend their future investigation in oral cancer management.

A review of the current evidence for the role of minimally invasive pancreatic surgery following neo-adjuvant chemotherapy

Objective:Surgical resection of pancreatic cancer remains the only potentially curative treatment for pancreatic ductal adenocarcinoma.The robotic platform has been introduced to surgical practice and recent large studies from national registries have demonstrated similar or improved peri-operative outcomes compared to the standard open approach.Neo-adjuvant chemotherapy is increasingly being offered to patients with borderline resectable/locally advanced disease but this has led to more challenging resections.Numbers of patients undergoing minimally invasive resection following neo-adjuvant chemotherapy remain low.The aim of this review is to assess the current evidence for the peri-operative safety and long-term oncological outcomes associated with minimally invasive pancreatic resection following neo-adjuvant chemotherapy.Methods:Medline,Embase and Cochrane Central Register for Clinical Trials were searched up until 31st October 2021.The search terms include“minimally invasive”,“robotic”,“laparoscopic”,“pancreatectomy”,“pancreatic resection”,“whipple's pancreaticoduodenectomy”,“distal pancreatectomy”,“chemotherapy”,“neo-adjuvant chemotherapy”,“radiotherapy”,“neo-adjuvant chemoradiotherapy”,“induction therapy”,and“conversion surgery”.All studies including patients undergoing pancreatic resections were included.Studies which did not clearly state the approach to resection(minimally invasive or open)were excluded.Results:Seventy-eight studies were identified of which 8 compared open and minimally invasive resection following neo-adjuvant chemotherapy.There was insufficient data to perform a meta-analysis.Robotic surgery was associated with lower blood loss and shorter length of hospital stay.Three-year overall survival rates were similar between patients who underwent robotic or open resection however the robotic approach was associated with higher lymph node yield and a lower R1 resection rate.Conclusion:Currently the evidence for minimally invasive surgery following neo-adjuvant chemotherapy is limited.Long-term oncological outcomes are similar to patients undergoing open resection and there is some evidence to suggest superior peri-operative outcomes.As numbers are limited,future studies analysing national and international databases on minimally invasive pancreatic resection are required to provide sufficient evidence to support the use of minimally invasive pancreatic resection following neo-adjuvant chemotherapy in high-risk groups.

Role of Neo-Adjuvant Chemotherapy in the Treatment of Osteosarcoma

Osteosarcoma is a tumour characterized by the production of osteoid by malignant cells. The incidence is approximately 1 to 3 million/year. The incidence is slightly higher in males. Onset can occur at any age;however, primary high grade osteosarcoma usually occurs in the second decade of life. Historically patients with osteosarcoma were treated with immediate wide or radical amputation. Despite the treatment, 80% patients with apparently isolated disease died of distant metastases. In recent years the number of patients with osteosarcoma of the limb treated by amputation + chemotherapy has increased. In our study, we divided the patients into two groups. One group (A) was treated with amputation + adjuvant chemotherapy. The other group (B) was treated with neo-adjuvant chemotherapy + amputation followed by adjuvant-chemotherapy. In our study, the margin negativity in post surgical specimen was significantly higher (P-value 0.0007) for the group treated with neo-adjuvant chemotherapy. Local recurrence in the group treated without neoadjuvant chemotherapy was significantly more (P-value 0.0005).The systemic recurrence at the end of 6 months was higher the group treated without neoadjuvant chemotherapy (P-value 0.0169).However systemic recurrence between 6 months -1 year and 1 year - 2 years were not significant(P-values 0.1501 and 0.4902). From the above figures it may be concluded that treatment with neo-adjuvant chemotherapy + amputation + adjuvant chemotherapy had definite advantages over upfront amputation + adjuvant chemotherapy.)

Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules.

Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation:Where do we stand?

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept “ablate and wait” has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of “ablate and wait” in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.

Colorectal cancer with liver metastases:Neoadjuvant chemotherapy,surgical resection first or palliation alone?

Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for > 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.

Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment

Epithelial ovarian cancer （EOC） is one of the most com-mon malignancies and one of the principal causes of death in gynecological neoplasms. The majority of EOC patients present with an advanced International Fed-eration of Gynecology and Obstetrics stage disease. The current standard treatment for these patients con-sists of complete cytoreduction and combined systemic chemotherapy of a platinum agent and paclitaxel. Even if the majority of patients with EOC respond to frst-line platinum based chemotherapy, almost 20% of them are resistant or refractory. According to these data, the main risk is for a certain number of patients to have undergone cytoreductive surgery （CRS） and subsequent hyperthermic intraoperative peritoneal chemotherapy （HIPEC） in a useful way. Radical surgery, especially in advanced cases, is associated with a high incidence of postoperative morbidity and mortality, which could be increased by the HIPEC. Every effort should be made for previously selected patients to improve outcome and optimize resources. Over the last decade, new options have been introduced to prolong survival. Im-proved long-term results can be achieved using CRS in combination with intraoperative HIPEC. This combina-tion has also been used in an up-front setting. Contro-versial outcomes have been reported for neoadjuvant platinum-based chemotherapy. Different papers have been published reporting discordant results. Further studies are needed.

Accuracy of physical examination, ultrasonography, and magnetic resonance imaging in predicting response to neo-adjuvant chemotherapy for breast cancer

Background Accurate evaluation of response following chemotherapy treatment is essential for surgical decision making in patients with breast cancer. Modalities that have been used to monitor response to neo-adjuvant chemotherapy （NAC） include physical examination （PE）, ultrasound （US）, and magnetic resonance imaging （MRI）. The purpose of this study was to evaluate the accuracy of PE, US, and MRI in predicting the response to NAC in patients with breast cancer. Methods According to the response evaluation criteria in solid tumors guidelines, the largest unidimensional measurement of the tumor diameter evaluated by PE, US, and MRI before and after NAC was classified into four grades, including clinical complete response, clinical partial response, clinical progressive disease, clinical stable disease, and compared with the final histopathological examination. Results Of the 64 patients who received NAC, the pathologic complete response （pCR） was shown in 13 of 64 patients （20%）. The sensitivity of PE, US, and MRI in predicting the major pathologic response was 73%, 75%, and 80%, respectively, and the specificity was 45%, 50%, and 50% respectively. For predicting a pCR, the sensitivity of PE, US, and MRI was 46%, 46%, and 39%, respectively, and the specificity was 65%, 98%, and 92% respectively. Conclusions Compared with final pathologic findings, all these three clinical and imaging modalities tended to obviously underestimate the pCR rate. A more appropriate, universal, and practical standard by clinical and imaging modalities in predicting the response to neo-adjuvant chemotherapy in vivo is essential.

Application of Aidi Injection (艾迪注射液) in the Bronchial Artery Infused Neo-Adjuvant Chemotherapy for stage ⅢA Non-small Cell Lung Cancer before surgical Operation

Objective： To study the effect of Aidi Injection （艾迪注射液,ADI） applied in the bronchial artery infused （BAI） neo-adjuvant chemotherapy for stage ⅢA non-small cell lung cancer （NSCLC） before surgical operation.Methods： The 60 patients with NSCLC stage ⅢA underwent two courses BAI chemotherapy before tumor incision were assigned to two groups,the treatment and the control groups,using a random number table,30 in each group.ADI （100 mL） was given to the patients in the treatment group by adding into 500 mL of 5% glucose injection for intravenous dripping once daily,starting from 3 days before each course of chemotherapy,and it lasted for 14 successive days,so a total of 28 days of administration was completed.The therapeutic effectiveness and the adverse reaction that occurred were observed,and the levels of T-lymphocyte subsets,natural killer cell activity,and interleukin-2 in peripheral blood were measured before and after the treatment.Results： The effective rate in the treatment group was higher than that in the control group （70.0% vs.56.7%,P〈0.05）.Moreover,as compared with the control group,the adverse reaction that occurred in the treatment group was less and mild,especially in terms of bone marrow suppression and liver function damage （P〈0.05）.Cellular immune function was suppressed in NSCLC patients,but after treatment,it ameliorated significantly in the treatment group,showing significant difference as compared with that in the control group （P〈0.05）.Conclusion： ADI was an ideal auxiliary drug for the patients in stage ⅢA NSCLC received BAI neo-chemotherapy before surgical operation;it could enhance the effectiveness of chemotherapy,ameliorate the adverse reaction and elevate patients＇ cellular immune function;therefore,it is worthy for spreading in clinical practice.

乳腺癌新辅助化疗前后X线征象的变化及意义

目的:对乳腺癌新辅助化疗(NCT)前后各种钼靶X线征象进行观察分析,以评价其疗效。方法:对比分析47例乳腺癌NCT前后钼靶摄影各主要征象的变化。结果:肿块变化发生率89.3%(42/47),其中类圆形肿块变化87.5%(7/8)、形态变化趋向不规则;模糊肿块93.7%(15/16)肿块边缘趋于清晰;肿块周围毛刺90.5%(19/21)变短甚至消失;透亮环肿块(1/2)可见瘤性实体缩小;病灶钙化74.2%(23/31)出现范围、数目、分布上的变化。结论:乳腺癌NCT前后钼靶摄影各种X线征象均有所变化。

Primary malignant melanoma of uterine cervix: a suggestion of new scheme of treatment combination

Historically, the lack of melanocytes in the vaginal and cervical mucus membranes has deterred the findings of primary melanomas. Mainly due to its rarity, difficulty to diagnose, and poor prognosis, there has been no absolute agreement on comprehensive treatment so far. In this case report, we present a case of a 46-year-old woman with primary malignant melanoma of uterine cervix. She underwent neo-adjuvant chemotherapy initially followed by a radical hysterectomy. After adjuvant concurrent chemo-radiation, the patient has been followed up for 24 months. So far, she has not shown any symptoms or signs of recurrence. Further studies with more cases based on variable combinations of treatment regimen have been on the way.

Adjuvant therapy for gastric cancer:Current and future directions

The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early,a large proportion of patients are diagnosed with loco-regionally advanced disease,resulting in high locoregional and distant relapse rates,with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing;however,randomized trials have now established either post-operative chemoradiotherapy(INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain,however,significant differences in the approach to management between the West and East. In Asia,where there is the highest incidence of gastric cancer,extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma,as well as recent and ongoing trials investigating novel(neo)adjuvant approaches,which hope to build on the successes of previous studies.

A Multidisciplinary Approach to the Treatment of Gastric Cancer: What Is the Role of the Surgeon?

Despite recent declining incidence, gastric cancer remains one of the most common cancers worldwide. Its treatment involves a multidisciplinary team to ensure implementation of investigated pre-operative and post-operative treatment strategies to improve survival. Our aim is to discuss the current role of the surgeon in improving survival of gastric cancer patients.