Waiting Time following Neoadjuvant Chemoradiotherapy for Rectal Cancer: Does It Really Matter.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer. However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable. OBJECTIVE AND METHODS: We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment. We used two alternative groups for analysis: patients who underwent surgery up to 6 weeks after CRT (n = 28) and those who underwent surgery 6 weeks or more after CRT (n = 27). Also, we compared patients who were operated on within 3 months (n = 39) with those who underwent surgical resection after more than 3 months (n = 16). Nonresponders to CRT were excluded from the analysis. RESULTS: There was no statistically significant association between waiting period post CRT and radiological downstaging for any group (p > 0.05 for any association). Also, there was no association between recurrence of disease, cancer-related deaths, perineural invasion, or positive lymph node ratio and any waiting period up to 3 months (p > 0.05 for all associations). CONCLUSION: In this small exploratory study there was no evident difference in outcome according to timing of surgery, which suggests that further research in larger cohorts is warranted.

The Concept of Hormesis in Cancer Therapy - Is Less More?

There has, in recent years, been a paradigm shift in our understanding of the role of the immune system in the development of cancers. Immune dysregulation, manifesting as chronic inflammation, not only facilitates the growth and spread of tumors but prevents the host from mounting effective immune defenses against it. Many attempts are being made to develop novel immunotherapeutic strategies, but there is growing evidence that a radical reevaluation of the mode of action of chemotherapeutic agents and ionizing radiation is required in the light of advances in immunology. Based on the concept of hormesis - defined as the presence of different modes of action of therapeutic modalities at different doses - a 'repositioning' of chemotherapy and radiotherapy may be required in all aspects of cancer management. In the case of chemotherapy, this may involve a change from the maximum tolerated dose concept to low dose intermittent ('metronomic') therapy, whilst in radiation therapy, highly accurate stereotactic targeting enables ablative, antigen-releasing (immunogenic) doses of radiation to be delivered to the tumor with sparing of surrounding normal tissues. Coupled with emerging immunotherapeutic procedures, the future of cancer treatment may well lie in repositioned chemotherapy, radiotherapy, and more localized debulking surgery.

Tumor Biology: Is It Time to Redefine Unresectability? An Extraordinary Case of Gastroesophageal Junctional Adenocarcinoma.

BACKGROUND: Disease assessment based on measurements of size and anatomic involvement have historically been central to surgical strategy. We propose this to be an outdated concept, which should be replaced by a deeper understanding of tumor biology and careful treatment planning. Report of case: A 34-year-old male was diagnosed with a Siewert Type 3 locally advanced cancer of the gastroesophageal junction, involving the coeliac axis and the superior mesenteric artery (SMA). He was treated with neoadjuvant chemotherapy, followed by chemoradiation, and then proceeded to surgery, at which time the tumor was judged unresectable. After extensive planning, a further surgery was attempted - an extended gastrectomy with distal esophagectomy, left hepatectomy, and splenectomy were performed. Additionally, the coeliac axis and the SMA were excised, followed by reconstruction of the hepatic artery and the SMA with grafts. Adjuvant chemotherapy was administered, and the patient is recurrence-free after five years follow-up. CONCLUSION: This case highlights the importance of the distinction between resectability and operability, and that patient treatment should be tailored and individualised based on the response to treatment, comorbidities, and underlying tumor biology.

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​.