Next-Generation Sequencing of Circulating Tumor DNA Can Optimize Second-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer after Progression on anti-EGFR Therapy: Time to Rethink Our Approach.

BACKGROUND: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. SUMMARY: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. KEY MESSAGES: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Synthesis of Recommendations From 25 Countries and 31 Oncology Societies: How to Navigate Through Covid-19 Labyrinth.

INTRODUCTION: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak. METHODS: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies. RESULTS: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis. CONCLUSIONS: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.

Fournier Gangrene in a patient receiving chemo-radiation for rectal cancer.

We herein present a case of a 24-year-old patient with a cT4N+ rectal cancer who developed Fournier's gangrene (FG) 1 week after the completion of preoperative chemoradiotherapy. The patient was promptly referred to the surgical department where she was treated with antibiotics and repeated surgical debridement. FG is a rare and life-threatening situation that needs to be managed aggressively with no delay. The clinical image above is unique and characteristic of this clinical entity.

The ALPPS procedure as a novel "liver-first" approach in treating liver metastases of colon cancer: the first experience in Greek Cypriot area.

BACKGROUND: Despite recent advances in multimodality and multidisciplinary treatment of colorectal liver metastases, many patients suffer from extensive bilobar disease, which prevents the performance of a single procedure due to an insufficient future liver remnant (FLR). We present a novel indication for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a "liver-first" approach when inadequate FLR was faced preoperatively, in a patient with extensive bilobar liver metastatic disease of colon cancer origin. CASE PRESENTATION: A 51-year-old lady was referred to our center due to a stage IV colon cancer with extensive bilobar liver disease and synchronous colon obstruction. During the multidisciplinary tumor board, it was recommended to proceed first in a palliative loop colostomy (at the level of transverse colon) operation and afterwards to offer her palliative chemotherapy. After seven cycles of chemotherapy, the patient was re-evaluated by CT scans that revealed an excellent response (>30%), but the metastatic liver disease was still considered inoperable. Moreover, with the completion of 12 cycles, the indicated restaging process showed further response. Subsequent to a thorough review by the multidisciplinary team, it was decided to proceed to the ALPPS procedure as a feasible means to perform extensive or bilobar liver resections, combined with a decreased risk of tumor progression in the interim. CONCLUSIONS: All in all, ALPPS can offer a feasible but surgically demanding liver-first approach with satisfactory short-term results in selected patients. Larger studies are mandatory to evaluate short- and long-term results of the procedure on survival, morbidity, and mortality.

Vaccine strategies in the treatment of low-grade non-Hodgkin lymphoma.

Recent years have witnessed the development of a variety of promising immunotherapies for treating patients with B-cell non-Hodgkin's lymphomas. Each B lymphocyte expresses an immunoglobulin molecule that is the product of a unique combination of gene segments. B cell malignancy arises from one original B lymphocyte, and therefore all the members of a given lymphoma tumor population have the same unique immunoglobulin, which can serve as a target for immune therapy. When the idiotype (Id), or unique portion, of each immunoglobulin is used as a vaccine, antibodies and T cells can be induced and each can cause rejection of the tumor by the host. This special opportunity for tumor specificity is accompanied by the challenge of constructing a different vaccine for each patient. The first clinical trial of Id vaccination for lymphoma was initiated at Stanford University in 1988. Tumor cells obtained from lymph node sampling were fused with a myeloma cell line to generate a "hybridoma" producing large quantities of idiotype protein. Purified Id protein was then chemically coupled to keyhole limpet hemocyanin (KLH) and emulsified in an "oil-in-water" type immunologic adjuvant. The initial trial included patients with low-grade, follicular lymphoma, in first remission following chemotherapy. Among the first 32 vaccinated patients, roughly half (14/32) developed anti-Id immune responses. These were principally humoral responses rather than cellular responses. Long-term follow-up of these 32 patients has revealed that the development of an immune response is strongly correlated with prolonged freedom from disease progression interval and overall survival. Further trials have confirmed significant clinical benefit following Id vaccination. There is reason for excitement about the prospects for effective vaccine therapies for lymphoma as randomized Id vaccine trials commence and newer cell-based vaccine trials enter the clinic. As the clinical activity of lymphoma vaccines becomes established, it will be important to determine how to best integrate active vaccination approaches with standard therapeutic approaches.

Clinical value of bone remodelling markers in patients with bone metastases treated with zoledronic acid.

BACKGROUND: Bisphosphonates have an established role in the treatment of bone metastases from a variety of solid tumours. The objective response to anti-resorptive treatment cannot be evaluated by imaging techniques. A number of bone remodelling markers have been associated with bone metastases status; among them, urine and serum levels of N-terminal telopeptide of collagen type I (NTx) seem to have the best diagnostic accuracy. However, serum NTx has not yet been properly evaluated. PATIENTS AND METHODS: Seventy-one consecutive patients with newly diagnosed skeletal metastases were enrolled in this prospective study. All of them were treated with zoledronic acid at 4 mg, every 3 or 4 weeks. Serum NTx and bone-isoform of alkaline phosphatase (BAP) were measured by enzyme-linked immunosorbent assays at baseline and every 2 months thereafter. RESULTS: At baseline, serum NTx and BAP levels were significantly higher in patients with blastic than lytic bone lesions and in those with multiple rather than few bone site involvement. Forty-seven patients were followed for a median period of 139 days. Zoledronic acid resulted in a significant NTx reduction at first and second post-treatment evaluations (mean reduction of 43% at first evaluation); thereafter, mean NTx levels remained suppressed. In contrast, BAP levels did not show any significant changes. Bone disease progression resulted in a significant NTx elevation by an average of 69%. The initial response of NTx to zoledronic acid was correlated with the long-term clinical outcome of bone disease: patients with an initial NTx elevation had a significantly higher rate of bone disease progression compared to those with an initial NTx decline (66.7% versus 18.8%, p=0.001). Extraskeletal disease or bone irradiation did not influence NTx response. CONCLUSION: Serum NTx appears to be a useful marker in monitoring patients with skeletal metastases, as it is correlated with the type and bulk of bone disease and reflects bone disease progression. It is also useful in monitoring bisphosphonate therapy, while the initial response to this therapy seems to bear a prognostic significance for bone disease outcome.