Implementing stereotactic arrhythmia radioablation with STOPSTORM.eu consortium support: intermediate results of a prospective Israeli single-institutional trial.

BACKGROUND: Ventricular tachycardia (VT) is a life-threatening arrhythmia originating from the heart's ventricles. Traditional treatments include antiarrhythmic medications, implantable cardioverter-defibrillators (ICDs), and catheter ablation. Stereotactic body radiation therapy (SBRT) targeting the arrhythmogenic focus in the left ventricle-stereotactic arrhythmia radioablation (STAR)-is an emerging treatment and may offer a potential solution for patients with refractory VT. OBJECTIVE: We designed an interventional prospective clinical trial in Israel aligned with the STOPSTORM.eu consortium's benchmarks, recommendations, and directives to assess the safety and efficacy of STAR in patients with refractory VT. METHODS: Our phase I/II single-institutional trial was approved by the Ministry of Health of Israel for 10 patients, initially assessing safety in the first 3 patients. We included patients with ICDs experiencing symptomatic monomorphic VT after an inadequate response to previous therapies. The primary endpoints were treatment-related serious adverse events and a reduction in VT burden as assessed by ICD interrogation. Secondary outcomes included a reduction in antiarrhythmic medications and changes in quality of life. RESULTS: From August 2023 to August 2024, 3 patients underwent STAR treatment. The prescription dose was a single fraction of 25 Gy. Planning target volumes were 47.8, 49.7, and 91.8 cc, and treatment was successfully delivered with no grade 3 or higher adverse events reported. Over a follow-up period of 12 months for the first patient and 8 months for the second one, no VT events were recorded after treatment. The third patient died from progressive heart failure 3 months after treatment. Left ventricular ejection fraction remained stable, and no significant radiation-induced inflammatory changes were noted. CONCLUSION: The initial results of this trial suggest that STAR can reduce VT episodes in patients with refractory VT without severe adverse effects. The study highlights the importance of international collaboration and standardization in pioneering new treatments. Further follow-up and additional patient data will be necessary to confirm these findings and evaluate long-term outcomes, including potential adjustments to antiarrhythmic medication regimens.

Oncological outcomes and failure patterns of laser cordectomy in recurrent glottic cancer.

PURPOSE: Laser cordectomy is a widely accepted treatment modality for selected cases of early glottic cancers, but its role as a salvage treatment remains unclear. We aimed to investigate the oncological outcomes and failure patterns of salvage cordectomy. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent cordectomy for early glottic cancer between 2013 and 2022 at a tertiary referral center. The main outcome measures were overall survival, larynx-preservation rate, tracheostomy dependency rate, and disease-free survival. RESULTS: A total of 142 patients (mean age: 63 years, interquartile range [IQR]: 45-72, 123[86.9 %] males) were analyzed. There were 38 (26.8 %) recurrences after a mean of 22 months (IQR: 17-26). Among them, 25 (17.6 %) underwent salvage cordectomy, while 13 (9.1 %) received other salvage treatments (11[7.7 %] (chemo)radiotherapy and 2[1.4 %] total laryngectomy). In comparison to the other salvage treatments, salvage cordectomy demonstrated lower tracheostomy rates (0 vs. 31 %, p = 0.05), comparable 5-year disease-free survival (62 % vs. 54 %, p = 0.4), higher 5-year larynx preservation rate (92 % vs. 54 %, p = 0.02), and improved 5-year overall survival rate (84 % vs. 62 %, p = 0.01). Factors associated with salvage cordectomy failure were age >60 years (odds ratio [OR]: 1.3, 95 % confidence interval [CI]: 1.15-1.53), smoking continuation (OR: 3.73, 95 % CI: 3.5-4.4), heavy smoking (OR: 1.24, 95 % CI:1.07-2.15), and pT1b + (OR: 2.26, 95 % CI: 2.1-2.9). CONCLUSIONS: Salvage cordectomy offers favorable larynx preservation rates and oncological outcomes for recurrent disease amenable to conservative surgery. Smoking, advanced age, and advanced tumor stages are associated with salvage cordectomy failure.

Case series report: radiation-induced oropharyngeal carcinoma.

The incidence of radiation-induced secondary primary tumors (SPTs) is estimated to be between 1 and 20%. The oropharynx is not a common site for postradiotherapy head and neck SPTs. We describe the cases of eight patients, each with an SPT of the oropharynx. These developed after a long median latency of 17.7 years with each receiving two-dimensional radiation therapy and delivery of at least 5000 cGy per pharynx, except for one who was treated with IMRT. Tumor histological commonalities revealed squamous cell carcinoma p16 negative staining, local invasion, and limited lymphatic spread, with posterior wall of the oropharynx and the base of the tongue being the most common locations. Limited and challenging treatment options have been reported such as surgery, reirradiation, or clinical trials. Radiation-induced SP oropharyngeal carcinoma has unique clinical and pathological features. Patients with this disease have limited treatment options, which should be discussed in a multidisciplinary tumor board meeting. For this population, lifelong follow-up may help in early diagnosis and improve outcomes.

Case report: ado-trastuzumab as second-line treatment in HER2 positive salivary duct carcinoma.

The objective of this report is to present the use and efficacy of ado-trastuzumab as an advanced line of therapy in salivary duct carcinoma (SDC) patient. An 84-year-old gentleman diagnosed with metastatic salivary duct tumor harboring overexpressed human epidermal growth factor receptor-2 has gone through resection surgery. The first line of treatment included initial doublet chemotherapy combined with trastuzumab, which was continued later as maintenance. PET-CT follow-up for 4 years has demonstrated no evidence of disease. However, upon recurrence, use of Ado-trastuzumab emtansine was prompted as second-line of treatment. This targeted patient-tailored therapy has accomplished a complete response. The effectiveness of ado-trastuzumab emtansine was notable within a short time period of two treatment cycles leading to full recovery. Specific agents aimed at altered oncogenes should be considered as a potential drug of choice in neoadjuvant HER2 positive SDC.

Tyrosine kinase inhibitor treatment and long-term follow-up for metastatic malignant struma ovarii.

Metastatic malignant struma ovarii (MMSO) is a very rare disease (in the United States, less than one case in 10 million females annually). However, this incidence rate is due to a paucity of data regarding diagnosis, treatment, and follow-up. Herein, we describe the case of a 14-year-old female who presented with MMSO, which later metastasized and was followed up on for over 10 years. The patient underwent right oophorectomy surgery and was then treated with a combination of radioactive iodine followed by iodine scans to detect the absorption of radioiodine in the metastatic sites, and radiation therapy to treat skeletal lesions. She subsequently received treatment with the tyrosine kinase inhibitors (TKIs), sorafenib and then lenvatinib, as treatments for advanced disease, thereby achieving long-term disease stability. This case report, which adds to the limited data available on MMSO treatment, suggests that patients treated with a combination of radioactive iodine, radiation therapy, and TKIs can result in good responses and long-term overall survival.

Treatment after progression in the era of immunotherapy.

Immunotherapy represents a paradigm shift in oncology treatment. The goal of immunotherapy is to overcome immunosuppression induced by a tumour and its microenvironment, thereby allowing the immune system to target and kill cancer cells. The immunotherapy era began when the first immune checkpoint inhibitor, ipilimumab, was approved for use almost a decade ago. This therapeutic approach is associated with distinct types of response, including processes such as pseudoprogression (ie, increased tumour burden via radiology, which is not accompanied by clinical deterioration) and hyperprogression (ie, rapid progression of the disease as a result of immunotherapy). In this Review, we focus on therapeutic approaches for patients who progress on immunotherapy. We review the different types of clinical responses associated with immunotherapy and describe treatment options for this population.

Perineural Invasion is a Better Prognostic Indicator than Lymphovascular Invasion and a Potential Adjuvant Therapy Indicator for pN0M0 Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) at pN0M0 can be more locally aggressive and disseminated than those with lymph node and distant metastasis. Perineural invasion (PNI) is reported as a poor prognostic factor in cancer and is thought to be related to regional tumor spread and metastasis. However, its clinicopathological role and meaning for treatment in pN0M0 ESCC are unknown. PATIENTS AND METHODS: We applied scoring methods of PNI and lymphatic and vascular invasion (LI, VI) based on immunohistochemistry staining on tumor tissues of pN0M0 ESCC patients. ROC analyses, Kaplan-Meier analyses, Cox regression, and χ2 test were performed for survival analysis, comparison of PNI with LI and VI, and exploration of the relevance between PNI and other clinicopathological features. RESULTS: Presence of PNI was significantly associated with poor survival in pN0M0 patients, whereas LI and VI were not predictive of outcome (P > 0.05). Neural invasion index (NII), defined as the ratio of the number of tumor-invaded nerves to the total number of nerves per tumor microsection, was the most consistent measure of PNI (P = 0.006, HR = 6.892, 1.731-27.428). Postoperative radiotherapy significantly improved survival in high-NII patients (P = 0.035, HR = 0.390, 0.163-0.936). CONCLUSIONS: PNI is an important risk factor for the outcome of pN0M0 ESCC patients. NII can be used for risk assessment and to tailor adjuvant radiotherapy in this population.

Precision medicine in head and neck cancer.

Head and Neck cancer is among the most common cancers worldwide, with a high prevalence in south East Asia, Brazil and central Europe. Head and Neck Squamous cell carcinoma (HNSCC) is associated with elevated mutational load but lacks specific genetic mutations. Exposure to carcinogens including tobacco and alcohol are the most dominant etiologic factors of HNSCC, while Epstein-Barr (HBV) and Human Papilloma Viruses (HPV) are associated with nasopharyngeal and oropharyngeal carcinoma, respectively. Surgery including open and minimally invasive procedures is considered the standard of care for the majority of oral cavity and early larynx cancers, while radiation therapy or concurrent chemoradiation are used for the other head and neck cancers. The treatment of patients with head and neck cancer is complex and has undergone considerable transformation in the last decade. These modalities include immunotherapy, targeted therapy (small molecule inhibitors or antibodies), or combined modality treatments. Emerging evidence supports a vital role of the immune system in eradicating HNSCC. Cancer cells express programmed death ligand 1 or 2 (PD-L1/2) which binds to the PD receptor on the T-cell, leading to an inactivation of the cytotoxic response of the T-cell. Cytotoxic T lymphocytes antigen-4 (CTLA-4) is another key player, expressed by cancer-activated T-cells, which binds to B7 ligand on the cancer cells, leading to inhibition of T-cells activation. Checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 antibodies, were shown to significantly improve disease free survival and overall survival after failure of platinum-based chemotherapy. In addition, expression of HPV is associated with better response to single modality treatment (e.g. radiotherapy or surgery) and improved survival. In future years we expect to see the establishment of precision medicine modalities in an attempt to extend survival and improve quality of life of advanced stage HNSCC patients. Several phase III clinical trials are in progress to evaluate the utility of checkpoint inhibitors at different treatment settings, including combinations with adjuvant surgery, radiation therapy and chemotherapy.

[SURGICAL TREATMENT OF LOCALLY ADVANCED WELL DIFFERENTIATED THYROID CARCINOMA].

AIMS: We aimed to better define the most appropriate therapeutic protocol for this type of tumor. BACKGROUND: The incidence of well-differentiated thyroid carcinoma is rising and the mortality from the disease remains low for patients with early disease. Nevertheless, the survival of patients with advanced disease has not improved during the last four decades and a controversy still exists in the literature regarding the optimal treatment in patients with locally advanced (T4) differentiated thyroid carcinoma. METHODS: Meta-analysis of the literature and our institutional experience, in treating patients with advanced papillary/follicular thyroid carcinoma. The main outcome measures were overall survival (OS) and disease-specific survival (DSS). RESULTS: The study group consisted of 38 patients with locally advanced thyroid carcinoma (T4). Regional spread to nodal metastases was present in 25 (65.7%) patients. Tracheal invasion was diagnosed in 29 (76.3%), of those 10 (26.3%) patients had airway obstruction. Recurrent laryngeal nerve (RLN) paralysis was revealed with clinical evidence during diagnosis in 23 (60.5%) patients. The 5-years OS was 66% and DSS was 87%. Multivariate analysis of outcome showed that undifferentiated carcinoma foci and vocal cord paralysis were associated with significantly reduced 5-years OS, and vocal cord paralysis was the only independent prognostic variable for DSS. Male gender and adjuvant radioactive iodine treatment were significant prognostic variables for disease free survival but not OS or DSS. CONCLUSIONS: Surgical resection remains the mainstay of treatment for locally advanced differentiated thyroid cancers. Foci of poorly differentiated cells, vocal cord paralysis and male gender are associated with poor prognosis. Radioactive iodine treatment improved local control but did not not affect OS. These patients should be managed by a multidisciplinary team in university centers specializing in treating complicated cancer patients.

Toxicity of Treatment for Anal Carcinoma: 2D versus 3D Planning.

BACKGROUND: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. OBJECTIVES: To summarize a single-center experience in the treatment of anal carcinoma using various radiation techniques. METHODS: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B). RESULTS: A total of 42 patients--25 (59.5%) females and 17 males (40.5%)--underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups; only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. CONCLUSIONS: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions but did not differ from 3D with regard to treatment efficacy.

Outcome of patients undergoing salvage surgery for recurrent nasopharyngeal carcinoma: a meta-analysis.

BACKGROUND: The common treatment of primary patients with nasopharyngeal carcinoma is chemotherapy and radiotherapy. Surgery is reserved as salvage procedure for recurrent or persistent disease. Nevertheless, information on the outcome of these patients and the role of adjuvant reirradiation treatment is scarce. METHODS: We conducted a meta-analysis to identify prognostic factors associated with outcomes of patients with recurrent nasopharyngeal carcinoma treated by salvage surgery. RESULTS: The study group consisted of 779 patients from 17 published studies who met the inclusion criteria. The primary tumor classification at recurrence was T1-2 in 83 % of patients and T3-4 in 16.6 %. Regional lymph node metastases were present in 88 patients. The 5-year overall survival and local recurrence-free survival rates of the entire cohort were 51.2 and 63.4 %, respectively, with a distant metastases rate of 11.3 %. The 5-year overall survival was 63 % in patients receiving surgery and adjuvant radiotherapy compared to 39 % in patients receiving surgery alone (P = 0.05). Independent predictors of outcome on multivariate analysis were sex, N classification, surgical approach (endoscopic vs. open), adjuvant treatment, and margin status. Both endoscopic surgery and reirradiation were independent predictors of improved survival. CONCLUSIONS: More than half of the patients with recurrent disease can be salvaged by surgery. Margins status, and N and T classification are significant predictors of outcome. Multivariate analysis revealed that endoscopic surgery offers better outcome than open surgery for T3/4 disease in selected patients, and adjuvant reirradiation offers an additional survival advantage over surgery alone.

Minimal clinically important differences in quality of life scores of oral cavity and oropharynx cancer patients.

BACKGROUND: The minimal clinically important difference (MCID) is defined as the smallest difference in quality of life (QOL) that patients perceive as beneficial and that mandates a change in management. We aimed to determine the MCID among patients with oral cavity and oropharyngeal cancer and to identify domains that are significantly affected during treatment. METHODS: The cohort consisted of 1,011 patients analyzed by a metaanalysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MCID values for the University of Washington Quality of Life Questionnaire (UW-QOLQ) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC C-30) and Head and Neck-35 questionnaires were calculated by using the distribution-based method. RESULTS: The mean MCID for Global QOL was 13.07 points for the UW-QOLQ and 9.43 in the EORTC C-30 questionnaire. High consistency in the MCID values was found between the two questionnaires examined. Heat map analysis indicated a clinically significant improvement in head and neck-associated domains and in domains associated with general cancer treatment 1 year or more after treatment relative to 3 months after treatment (p < 0.001 and p = 0.016, respectively). In contrast, improvement in general and functional domains was not evident 1 year or more after treatment (p = 0.69). CONCLUSIONS: This study suggests benchmark values for MCID and variation in QOL scores of oral and oropharyngeal cancer patients after treatment. Improvement in head and neck- and general cancer-associated domains may not be translated into a general and functional improvement during the first year of recovery.

Rectal adenocarcinoma in the eye: An unexpected destination.

Colorectal cancer ranks third in cancer incidence in the United States, commonly metastasizing to the liver and lungs. Despite its high prevalence, colorectal cancer with intraocular metastasis is exceedingly rare, with only a few cases reported in the literature. This study presents a 58-year-old male, previously treated for rectal adenocarcinoma with liver and lung metastases, who developed choroidal metastasis causing visual impairment. Despite radiotherapy, moderate improvement was observed, and subsequent disease progression led to systemic chemotherapy. Intraocular metastasis, primarily affecting the choroid, is infrequent, often originating from breast and lung cancers. The presented case, originating from primary KRAS wild-type rectal cancer, adds to the limited gastrointestinal-tract-related occurrences. This report underscores the importance of recognizing intraocular metastasis in colorectal cancer, contributing valuable insights for improved understanding and potential guidance for future clinical decisions. Choroidal metastasis carries a poor prognosis, emphasizing the need for tailored management strategies.

Changing the paradigm: Elimination - Not only of cervical cancer.

The WHO's initiative to eliminate cervical cancer by 2030 does not address the increasing incidence of vulvar, anal, and oropharyngeal cancers linked to high-risk HPV. Currently, the prevention of these three cancers faces various obstacles, such as a lack of specialized screening programs, well-defined management guidelines, and widespread public awareness. Without any interventions, the incidence of these three cancers will likely rise in the upcoming years, increasingly affecting younger individuals. We recommend expanding the WHO's initiative to include vulvar, anal, and oropharyngeal cancers. This involves developing screening and management protocols similar to those for cervical cancer, implementing gender-neutral HPV vaccination programs, establishing clear referral pathways to specialized centers, promoting public awareness, and providing education to healthcare providers and high-risk individuals.

PD1 ligand functionality a biomarker of response to anti PD1 treatment in patients with HNSCC.

Therapies targeting the PD-1/PD-L1 pathway have transformed head and neck squamous cell carcinoma (HNSCC) treatment. However, predicting the response to anti-PD-1 therapy remains a clinical challenge. This study evaluated the functional binding of PD-1 ligands in 29 HNSCC patients and compared it to the standard PD-L1 Combined Positive Score (CPS). The assessment of PD-1 ligands' functionality advances the current ability to predict the response of HNSCC patients to anti-PD-1 therapy.