The Journal of Bucharest College of Physicians and the Romanian Academy of Medical Sciences

Camil Ciprian Mirestean

Camil Ciprian Mirestean

Skin Cancers of the Head and Neck Region: the Real World Epidemiological and Therapeutic Data from the Cancer Registry of Dolj County

The majority of skin cancers of the head and neck are represented by basal cell carcinoma (BCC) and cutaneous squamosal cell carcinoma (CSCC), both non-melanoma skin cancers. Identified in the early stages, the cure rate is considered high. Sun protection and early identification of suspicious lesions are the optimal strategies for these cancers to be associated with higher response rates and favorable cosmetic results. Even if the incidence is lower, 10% to 25% of melanomas could also be identified in the head and neck region. For advanced stages or for cases ineligible for optimal surgical treatment, the multimodal approach including adjuvant radiotherapy, chemotherapy, biological therapy or immunotherapy must be decided in a multidisciplinary team. We set out to retrospectively evaluate the data of patients with skin tumors in the head and neck region included in the cancer registry of Dolj county between January 2000 and December 2019. Seventy-three patients were subsequently identified who met the inclusion criteria. The median age of the patients was 73 years (46 to 98). Forty-six cases of these were BCC, 15 CSCC cases, 1 adenoid cystic carcinoma case, 1 malignant melanoma case and one case without histopathological confirmation. The ratio between BCC and CSCC in our study is 3:1, in concordance with the ratio identified in the literature. The vast majority of cases come from the urban environment, surgery being the main treatment, especially for the early stages. Adjuvant radiotherapy was administered both in cases of BCC and epidermoid carcinoma. Adjuvant polychemotherapy, interferon therapy and re-irradiation have also been used. Considering the main risk factor, exposure to the sun, it is possible that the predominance of cases from cities is caused by underreporting of these types of cancer in rural communities where the main occupation is agriculture, associated with sun exposure, but also by a lower addressability or non-compliance with the inclusion in the oncological monitoring programs. The current existence of some modern oncological therapies, including immunotherapy for CSS and malignant melanoma, justifies a better monitoring and inclusion of these cases in multidisciplinary evaluation. Superficial radiotherapy, which has now become less accessible in our country, due to the implementation of radiological safety rules and the conversion of equipment from the former Soviet Union cobalt and superficial X-ray radiotherapy device to modern liniac accelerators focused on modern techniques radiotherapy is necessary to reduce the risk of recurrence in the case of resection with inadequate margins of non-melanoma skin tumors.

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Cetuximab-Taxanes-Platinum-Fluorouracil/ Capecitabine (C-TPF/C-TPX) – a Feasible Option for Recurrent HNSCC with Negative Prognostic Factors. Literature Review with a Case Presentation

Concurrent chemo-radiotherapy with Cisplatin is the standard treatment for locally advanced non-metastatic squamous cell carcinoma of the head and neck (HNSCC), but induction chemotherapy (IC) followed by chemo-irradiation, even controversial is a widely accepted option, especially in high- risk cases. A regimen including triple association (platinum-taxanes-fluorouracil) is generally considered superior in efficacy, but may be associated with severe toxicity. In the case of recurrence, the options are limited and the prognosis is generally unfavorable. Chemotherapy alone or in combination with an anti-EGFR monoclonal antibody (Cetuximab), immunotherapy or re-irradiation for selected cases are feasible options in loco-regional or metastatic repalapse. We present a case of nasopharyngeal cancer (NPC), with negative prognostic and predictive factors multimodally treated with an intensive chemotherapy regimen associating Cetuximab with a median survival higher than the median value reported in most studies. Replacing 5-Floururacil with Capecitabine and Cisplatin with Carboplatin may be an option to increase treatment tolerance and should be evaluated in randomized trials. The use of induction chemotherapy as a “new standard” before radio-chemotherapy for cases with negative prognostic factors should also be the subject of future studies. Re-challenge with platinum is also an option that needs to be re-evaluated.

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Delta-radiomics Entropy Based on Tumor Heterogeneity Concept – Response Predictor to Irradiation for Unresectable/recurrent Glioblastoma

Although adjuvant radiotherapy in combination with Temozolomide administration has clearly demonstrated the benefit in improving the prognosis of patients with multiforme glioblastoma, radiotherapy as only treatment or in combination with systemic treatment is one of the best supportive in unresectable cases. For recurrent cases, the salvage radiotherapy option (re-irradiation) can be chosen in carefully selected cases so that the benefit is greater than the toxicities. Radiomics, a new subdomain of artificial intelligence (AI), relies on advanced analysis in high-resolution medical imaging to establish diagnostic, prognostic and predictive models for clinical medicine. The variation of the delta-radiomics parameters analyzed within a tumor volume may be via tumor heterogeneity indirectly correlated with the response to treatment. The aim of the study is to propose a delta-radiomic based on entropy algorithm to allow the non-invasive pre-therapeutic identification of patients with unresectable or recurrent multiform glioblastoma who will benefit from irradiation and/or salvage re-irradiation.

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Targeting EGFR Exon 20 Insertion-mutated Cancers – New Perspectives in Head and Neck Cancers – Lessons to Learn from Non-small Cell Carcinoma (NSCLC)

Mutations in the tyrosine kinase (TKD) domain of the epidermal growth factor receptor (EGFR) are involved in the unfavorable therapeutic response through resistance to targeted molecular therapy. Data from the clinical experience of non-small cell lung carcinoma (NSCLC) treatment demonstrate the benefit of tyrosine kinase inhibitors (TKIs) in cases of EGFR mutation. The next generation sequencing technique (NGS) allows the identification of hot spots involved in mutations, exon 20 insertion being associated with the unfavorable response. Exon 20 insertions are more common in head and neck squamous cell carcinoma (HNSCC) compared to NSCLC, which could explain a resistance to targeted therapy in head and neck cancers. Taking into account the data reported in the NSCLC, Amivantamab, a bi-specific EGFR-MET antibody with potential immune cell modulation of activity, but also other innovative therapies validated in exon20 EGFR mutation could be part of the therapy of sino-nasal cancer, but also of other HNSCC sites exon 20 mutant EFGR.

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Free Educational Android Mobile Application for Radiobiology. Evaluation of Radiation Oncologist and Medical Physicist

The use of mobile devices and applications dedicated to different medical fields has improved the quality and facilitated medical care, especially in the last 10 years. The number of applications running on the software platforms of smart phones or other smart devices is constantly growing. Radiotherapy also benefits from applications (apps) for TNM staging of cancers, for target volume delineation and toxicity management but also from radiobiological apps for calculating equivalent dose schemes for different dose fractionation regimens. In the context of the increasingly
frequent use of altered fractionation schemes, the use of radiobiological models and calculations based on the linear quadratic model (LQ) becomes a necessity. We aim to evaluate free radiobiology apps for the Android software platform. Given the global educational deficit, the lack of experts and the concordance between radiobiology education and the need to use basic clinical notions of modern radiotherapy, the existence of free apps for the Android platform running on older generation processors can transform even an old smart device in a powerful „radiobiology station.” Apps for radiobiology can help the radiation oncologist and medical physicist with responsibilities in radiotherapy treatment planning in the context of accelerated adoption of hypo-fractionation regimens and calculation of the effect of treatment gaps, a topic of interest in the COVID-19 pandemic context. Radiobiology apps can also partially fill the educational gap in radiobiology by arousing the interest of young radiation oncologists to deepen the growing universe of fundamental and clinical radiobiology.

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Palliative Re-Irradiation of Bone Metastases - Case Report

Bone metastasis is a severe complication of malignant tumors. Management of multiple bone metastases remains difficult and prognosis is generally unfavorable, radiotherapy being often the therapeutic option. The main goals of the palliative irradiation of bone metastases are the reduction of pain intensity and the decreasing the analgesic dose used. Overall survival of patients with oligometastatic disease for hormone dependent cancers like breast and prostate may exceed three years and for these groups of patients the reduction of the associated tardive toxicity after irradiation is essential for preserving the quality of life. We present the case of a patient diagnosed in March 2011 with prostate cancer, multiple bone metastases in November 2012. In December 2012, palliative radiotherapy was administrated in a total dose of 21Gy/fractions, weekly in the lumbosacral region. Seven years after the first presented an increase in pain intensity in the left ischio-pubian branch and pubic symphysis and the bone scintigraphy reveal the progression of the metastatic disease. Palliative re-irradiation was administrated in total dose of 20Gy/5fractions in painful region. Re-irradiation for bone metastasis remains a therapeutic option with the potential to reduce the pain. Image guided radiotherapy can reduce the risk of late toxicity, especially for long-term survivors.

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Modern Radiotherapy for Head and Neck Cancers Benefits and Pitfalls - a Literature Review

Curative radiotherapy is part of the multimodal treatment for locally advanced head and neck cancers. The technical revolution in the field of radiation therapy and medical imaging has made possible a better conformation of the target volumes with irregular shapes with a dose reduction at the radiosensitive organs in the vicinity. Three-dimensional Conformal Radiotherapy (3D-CRT) has been replaced by Intensity Modulated Radiotherapy (IMRT), and more recently the Intensity Modulated Volumetric Arc Therapy (VMAT) technique is being used on an ever-expanding scale as a replacement for the „step and shot” IMRT technique. The benefits of the IMRT/VMAT techniques were mainly consisting of a better conformation for the target volumes with irregular shapes and the reduction of acute and late xerostomia. The results in the tumor control are considered similar to those obtained by the 3D-CRT technique except for nasopharyngeal cancer in which the use of chemo-radiotherapy by the IMRT technique has led to an improved local survival and local and regional control rate. Increasing the incidence of HPV-positive head and neck cancers with a better prognosis and the need to improve quality of life would be an argument in favor of using treatments with a low toxicity profile. By reducing the dose of healthy tissue, the use of modern irradiation techniques opens new horizons for the re-irradiation with high radiation doses of recurrent head and neck tumors.

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Evaluation of the Diabetes Contribution to the Occurrence of Treatment Related Toxicities in Multimodal Treated Locally Advanced Head and Neck Cancers

Diabetes mellitus is often associated with a risk of developing some types of cancer. The association between head and neck cancers and diabetes as well as prognosis and treatment tolerance remains a controversy. Acute toxicities associated with treatment may be amplifi ed by the presence of comorbidities, including hypertension, diabetes and collagen diseases. Another factor implicated in the treatment tolerance is also the limitation by the presence of hyperglycemia of the corticosteroids dose used for the control of pain and edema associated with chemo-irradiation and for the treatment of thrombocytopenia. The purpose of the study was to evaluate the involvement of diabetes mellitus in the toxicities associated with chemo-radiotherapy treatment in multimodal treated patients for advanced local head and neck cancers. For patients with locally advanced non-metastatic head and neck treated with multimodal (chemo-radiotherapy) acute toxicities (radio-dermitis, radio-mucositis, dysphagia) was analyzed comparatively in patients who associate or not cancer with diabetes. It was also compared if the diagnostic of diabetes influenced the intensity of chemotherapy. Identifying the predictive value of diabetes mellitus for the severity of toxicities in multimodal curative treatment for head and neck cancers can lead to limitation of radiation dose to some radiosensitive anatomical structures in the context of the modern IMRT and VMAT irradiation techniques implementation in clinical practice.

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