Cardiac and Nephrological Complications Related to the Use of Antiangiogenic and Anti-Programmed Cell Death Protein 1 Receptor/Programmed Cell Death Protein 1 Ligand Therapy.

The ability to undergo neoangiogenesis is a common feature with all cancers. Signaling related to vascular endothelial growth factors (VEGF) and their receptors (VEGFR) plays a key role in the process of tumor neoangiogenesis. A close relationship has been demonstrated between excessive VEGF levels and the induction of immunosuppression in the tumor microenvironment. The use of drugs blocking the VEGF function, apart from the anticancer effect, also result in adverse effects, in particular related to the circulatory system and kidneys. Cardiac toxicity associated with the use of such therapy manifests itself mainly in the form of hypertension, thromboembolic episodes and ischemic heart disease. In the case of renal complications, the most common symptoms include renal arterial hypertension, proteinuria and microangiopathy. Although these complications are reversible in 60-80% of cases after cessation of VSP (VEGF pathway inhibitor) therapy, in some cases they can lead to irreversible changes in renal function, whereas cardiac complications may be fatal. Also, the use of PD-1/PD-L1 inhibitors may result in kidney and heart damage. In the case of cardiac complications, the most common symptoms include myocarditis, pericarditis, arrhythmia, acute coronary syndrome and vasculitis, while kidney damage most often manifests as acute kidney injury (AKI), nephrotic syndrome, pyuria or hematuria. The decision whether to resume treatment after the occurrence of cardiovascular and renal complications remains a problem.

Brachytherapy in the Treatment of Non-Melanoma Skin Peri-Auricular Cancers-A Retrospective Analysis of a Single Institution Experience.

The location of skin neoplasms in the area of the ears qualifies patients to the so-called high-risk group. The location of neoplasms within the auricle and around the ear often causes many problems in surgical treatment. This is due to the presence of cartilage, the difficulty of performing procedures with obtaining a visually satisfactory cosmetic effect, especially in the presence of extensive lesions and can lead to positive surgical margins which leads to a high risk of recurrence. In such cases, the use of brachytherapy, both as an independent method and as a complementary method after surgery, may be an effective method of local control with an acceptable risk of radiation complications. However, there are no large retrospective studies on the use of brachytherapy in this anatomical region. The aim of the study was to analyse the effectiveness, toxicity profile, and cosmetic effect of two different brachytherapy techniques (contact and interstitial brachytherapy). Methods: This paper presents the results of a retrospective analysis of 33 patients treated with contact or interstitial high-dose-rate (HDR) brachytherapy for skin cancers of the outer ear, involving the auricle and the skin of the adjacent area. Brachytherapy was used both as a definitive treatment (15 patients­43%) and adjuvant treatment after surgery (18 patients­57%). The basic criterion for adjuvant treatment was a positive or narrow (<1 mm) resection margin. Fraction doses from 3 to 7 Gy per fraction were used at intervals from six hours (interstitial brachytherapy) to a maximum of seven days (contact brachytherapy). The treatment time ranged from 1 to 42 days, and the total dose range was 7 to 49 Gy. The follow-up was 29.75 months (range 2−64). Results: In the group of patients treated with adjuvant therapy, in the patients with post-radiation reaction, the mean time from surgery to the start of brachytherapy was 7.72 ± 3.05 weeks, the median was 8 (6−12) weeks, and in the group without post-radiation reaction, the mean time was 11.13 ± 4.41 weeks, the median time was 11 weeks (8−14). The risk of a post-radiation reaction increased significantly more often in patients with more advanced disease. In the case of contact brachytherapy, the post-radiation reaction occurred significantly more often (14/21 patients­43%) than in the case of interstitial brachytherapy (3/11 patients­9.4%). In patients with post-radiation reactions, a significantly larger volume of the skin receiving a dose of 200% was found, and the volume receiving a dose of 150% was close to statistical significance. The mean volume of the skin receiving a 200% dose in the group with post-radiation reactions was 28.05 ± 16.56 cm3, the median was 24.86 (0.5−52.3) cm3, and the mean volume in the group without post-radiation reaction was 17.98 ± 10.96 cm3, median 14.95 (3.9−44.96) cm3. The result was statistically significant (Z = 2.035, p = 0.041). Conclusion: Interstitial HDR (high-dose-rate) brachytherapy for non-melanoma skin cancers around the ear is highly effective, short, and has a relatively low burden on the patient. The toxicity of the treatment was low. In the case of contact brachytherapy, the toxicity profile is slightly higher but acceptable for patients. This method is preferred in patients in whom interstitial brachytherapy is impossible to perform due to anatomical and logistical reasons. The unquestionable advantage of contact brachytherapy is its ability to be performed on an outpatient basis without the need to stay in the hospital. No severe and late CTCAE ≥III and late RTOG ≥III toxicity was observed. In patients after surgery, in order to minimise the risk of radiation reaction, it is optimal to start treatment at least eight weeks after surgery. In the presence of extensive lesions, the use of interstitial brachytherapy seems to be more advantageous, especially when the expected volume of healthy skin in the dose range of 200% and 150% is above 15 cm3 and 50 cm3, respectively.

Outcomes of Patients with Metastatic Melanoma-A Single-Institution Retrospective Analysis.

Background: This study assessed risk factors and the results of treatment with anti-PD-1 antibodies and BRAF/MEK inhibitors for advanced malignant melanoma. Methods: A retrospective analysis was performed on 52 patients treated with immunotherapy and BRAF/MEK inhibitors for disseminated malignant melanoma. Results: The median follow-up was 31 months (6−108 months). The median PFS1 was 6 months (1−44 months). Second-line systemic treatment was applied in 27 patients (52%). The median PFS2 was 2 months (0−27 months), and the median OS was 31 months (6−108 months). Among the analyzed risk factors, only the presence of the BRAF mutation was statistically significant for disease recurrence after surgery. In patients undergoing anti-BRAF/MEK therapy, the median PFS1 was 7 months, and in patients undergoing mono-immunotherapy, 4 months. The 12- and 24-month PFS1 rates in the group treated with BRAF inhibitors were 29 and 7%, respectively, and in patients treated with mono-immunotherapy 13 and 0%, respectively (Z = 1.998, p = 0.04). The type of treatment used had no effect on OS (Z = 0.237, p > 0.05). Conclusion: Patients with the V600 mutation should be closely monitored. In the event of disease recurrence, treatment with BRAF/MEK inhibitors should be considered. The type of treatment used has no effect on OS.

Interstitial HDR Brachytherapy in the Treatment of Non-Melanocytic Skin Cancers around the Eye.

BACKGROUND: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications within ocular structures, especially the lens. In the case of interstitial brachytherapy, it is possible to administer a high dose to the clinical target volume (CTV), while reducing it in the most sensitive structures. METHODS: This paper presents the results of an analysis of 28 patients treated with interstitial high dose rate (HDR) brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral canthus; and the cheek, nose and temples with the infiltration of ocular structures. The patients were treated according to two irradiation schedules: 49 Gy in 14 fractions of 3.5 Gy twice a day for 7 days of treatment, and 45 Gy in 5 Gy fractions twice a day for 5 days. The mean follow-up was 22 months (3-49 months). RESULTS: two patients (6%) had a relapse: a local recurrence within the irradiated area in one of them, and metastases to lymph nodes in the other. The most common early complication was conjunctivitis (74%), and the most common late complication was dry eye syndrome (59%). CONCLUSIONS: Interstitial HDR brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral cants; and the cheek, nose and temples with infiltration of ocular structures is a highly effective, short and relatively low burden type of treatment.

The Role of Prognostic Factors in Salivary Gland Tumors Treated by Surgery and Adjuvant Radio- or Chemoradiotherapy - A Single Institution Experience.

PURPOSE: Salivary gland neoplasms are rare cancers of the head and neck region. Radical treatment in tumors of large salivary glands is surgery. Adjuvant treatment depends on the presence of risk factors that worsen the prognosis, but the role of these factors in patients treated by surgery with radio- or radiochemotherapy still remains unclear. The aim of the study is assessment of treatment results and identification of the risk factors affecting the prognosis in patients with tumors of large salivary glands subjected to adjuvant radio- or radiochemotherapy. PATIENTS AND METHODS: The study included 126 patients with local stage large salivary gland cancer who were treated surgically with adjuvant radio- or radiochemotherapy. The study excluded inoperable patients, patients with distant metastases, patients in a poor general condition and patients with contraindications to adjuvant treatment. They were treated between 2006 and 2016 and evaluated in terms of OS (overall survival), CSS (cancer-specific survival), RFS (relapse-free survival) and LRFS (local relapse-free survival). RESULTS: During a 44-month follow-up, 5-OS, CSS, RFS and LRFS were 55%, 68%, 60% and 73%, respectively. Multivariate analysis showed that OS was influenced by the following parameters: WHO performance status, TNM stage (T and N parameters), radicality of surgery, histopathological type, applied method of radiotherapy planning and tumor volume. WHO performance status, T and N parameters of the TNM stage and large volume of elective area influenced CSS, and the T parameter of the TNM stage, the dose below 60Gy and tumor volume influenced RFS and LRFS. Chemoradiotherapy can be used in N-positive patients. CONCLUSION: The analysis indicates that the TNM grade, histopathological type, patient's condition, radicality of the procedure, technique and dose of radiotherapy are the most important prognostic factors in these patients.

Treatment of hepatic metastases with computed tomography-guided interstitial brachytherapy.

The aim of the present study was to evaluate the efficacy, safety and tolerability of local treatment of liver metastases of various types of cancer using brachytherapy with computed tomography (CT) imaging. Retrospective analysis of 61 patients with unresectable hepatic metastases treated with CT-guided interstitial high dose rate (HDR) brachytherapy of the liver between April 2014 and December 2016 was performed. Patients were treated with a single fractional dose of 15-25 Gy. Statistical analysis was performed on local relapse free survival (LRFS), progression free survival (PFS) and overall survival (OS) rates across the group. In the 6 and 12-month follow-up periods, the 6- and 12-month LRFS rates were 88.7 and 70.7%, PFS rates were 78.1 and 53.8% and the OS rates were 96.7 and 79.6%, respectively. In the Cox regression analysis, the 100% isodose was a statistically significant predictor of LRFS (P=0.01) and PFS (P=0.02), but it was not significant in OS (P=0.07). The 90% isodose was a statistically significant predictor of LRFS (P=0,03) but not significant in PFS (P=0.17) or OS (P=0.25). In all patients, no serious complications were observed. Overall, 30% of patients experienced pain at the injection site, and 50% exhibited nausea or vomiting. In 2 patients, minor subcapsular bleeding occurred without clinical significance, and 1 patient was diagnosed with a pneumothorax that was not clinically significant. Brachytherapy HDR with CT imaging is an effective and safe method of local treatment of liver metastases. The effectiveness of the treatment is probably dose-dependent, and increases with increasing dosage.

Retrospective Analysis of Intravaginal Brachytherapy in Adjuvant Treatment of Early Endometrial Cancer.

The aim of this study was to determine the role of adjuvant endovaginal brachytherapy HDR (High Dose Rate) or observation, as well as identification of risk factors of tumor recurrence. The study included 178 women after radical hysterectomy. All patients belonged to the group of low- and medium-risk stage I FIGO. Analysis consisted of 3-, 5-, and 10-year OS, DFS, and LRFS in both groups. Follow-up was more than 6.5 years. The 5-OS, 5-DFS, and 5-LRFS were 93%, 96%, and 98% in the treated group and 95%, 94%, and 96% in the observed group, respectively. These differences were not statistically significant. There was a statistically significant difference in 5-OS in the treated group, between low- and medium-risk subgroups (100% versus 87.55%, p = 0.018). There was a better prognosis among the patients with FIGO IA compared to FIGO IB (5-DFS, 97 versus 86%, p = 0.047). Among the risk factors, there were only statistically significant differences in the 5-OS, between the ages of ≤ 70 years and >70 years. Use of brachytherapy may affect the reduction in the number of local recurrences at the vaginal stump (6% versus 2%). This is particularly noticeable in the low-risk subgroup (9% versus 0%).

[Gout or squamous cell cancer of the ear in a 91-year-old man - diagnostic and therapeutic problems: a case report].

Gout tophi around auricular area are common in old men. The differential diagnosis of papules or nodules on the ear includes tophaceous gout, rheumatoid nodules, basal or squamous cell cancer, melanoma, verruca vulgaris or actinic keratosis. The presence of the skin cancer, most commonly located on the head and neck, is often related to the long exposure of the skin to sunlight. Elderly patients are the predominant group of patients with skin malignancies. The aim of this study is to emphasize the importance of early cancer detection in elderly people and use of appropriate therapeutic options that take into account the special requirements of geriatric patients. In this article the case of a 91-year-old man with advanced gout and squamous cell cancer of the skin of the ear, treated radically with a positive clinical effect, is presented. Moreover, the diagnostic and therapeutic problems are presented.

Image-guided high-dose-rate brachytherapy of head and neck - a case series study.

PURPOSE: The aim of the study was the evaluation of image guided transdermal application of interstitial brachytherapy in patients undergoing repeated irradiation for relapsed local tumor of the head and neck area. MATERIAL AND METHODS: The article describes transdermal application of interstitial high-dose-rate (HDR) brachytherapy in 4 patients treated due to relapsed local tumor in soft palate, submandibular area, laryngopharynx, as well as pterygoid muscles and maxillary sinus. The application was conducted under continuous computed tomography (CT)-image guidance (CT fluoroscopy). Patients qualified for this type of treatment had neoplastic lesions located deep under the skin surface. Because of their location, access to the lesions was limited, and the risk of damaging the adjacent tissues such as vessels and nerves was high. The following parameters have been evaluated: clinical response using RECIST 1.1, incidence of perisurgical complications using CTCAE 4.0 and the frequency of occurrence of radiotherapy related early morbidity using RTOG. RESULTS: Various radiation schemes were used, from 3 to 5 fractions of 3.5-5 Gy. The median total dose (D90) was 20.6 Gy. Biologic effective dose (BED) and equivalent 2 Gy (DEQ2) median doses were 30.4 Gy and 25.3 Gy, respectively. In the follow-up period of 3-7 months (the median value of 3.5 months), 2 patients had partial regression of the disease and in 2 others the neoplastic process was stabilized. None of the patients had serious complications of treatment (of 3rd degree or higher). CONCLUSIONS: Computed tomography-image guided brachytherapy proved to be a safe method of treatment in patients with local relapse in sites, in which traditional visually controlled application was impossible due to risk of complications. Despite short observation period and small study group, it seems justified to conduct prospective studies for the evaluation of efficacy and safety of CT-image guided brachytherapy.

[Lymphoedema--diagnosis and treatment]. / Obrzeki limfatyczne--diagnostyka i leczenie.

Lymphoedema is a common complication of oncological treatment. Various methods of imaging are used in its diagnosing and monitoring. However, presently lymphoscintigraphy has become the golden standard. A physical examination and detailed medical history also play a very important role. There are still no effective methods of prevention and treatment of lymphoedema in spite of medical progress. The treatment requires a multidisciplinary approach with the use of various methods of physiotherapy (pressure therapy, pneumatic pumps and electric high-voltage treatment), pharmacology and surgery. Patient's education and suitable physical exercises are also significant.

[Radiation-induced neuropathy]. / Powiklania neurologiczne po radioterapil.

Radiation-induced neuropathy is commonly observed among oncological patients. Radiation can affect the nervous tissue directly or indirectly by inducing vasculopathy or dysfunction of internal organs. Symptoms may be mild and reversible (e.g., pain, nausea, vomiting, fever, drowsiness, fatigue, paresthesia) or life-threatening (cerebral oedema, increased intracranial pressure, seizures). Such complications are clinically divided into peripheral (plexopathies, neuropathies of spinal and cranial nerves) and central neuropathy (myelopathy, encephalopathy, cognitive impairment). The degree of neuronal damages primarily depends on the total and fractional radiation dose and applied therapeutic methods. The conformal and megavoltage radiotherapy seems to be the safeties ones. Diagnostic protocol includes physical examination, imaging (in particular magnetic resonance), electromyography, nerve conduction study and sometimes histological examination. Prevention and early detection of neurological complications are necessary in order to prevent a permanent dysfunction of the nervous system. Presently their treatment is mostly symptomatic, but in same cases a surgical intervention is required. An experimental and clinical data indicates some effectiveness of different neuroprotective agents (e.g. anticoagulants, vitamin E, hyperbaric oxygen, pentoxifylline, bevacizumab, methylphenidate, donepezil), which should be administered before and/or during radiotherapy.

[Chemotherapy induced peripheral neuropathy]. / Neuropatia obwodowa wywolana chemioterapia.

Modern cancer therapy prolongs patients life but commonly increases incidence of treatment-related complications. One of such adverse effect is a neurotoxicity, which usually manifestates as peripheral neuropathies (CIPN), characterised by various sensory (tingling, numbness, pain), motor (foot and hands drop, fastening buttons difficulties) and autonomic (constipation, arythmia) abnormalities as well as pain. Despite of intensive epidemiological and clinical studies, standardized diagnostic criteria and methods of the neuropathy prevention and treatment have not been fully established. The most commonly used form of treatment is symptomatic therapy, including anticonvulsant and antidepressant drugs. Proper education of patients and their families of symptoms and neuropathy consequences is desirable to reduce anxiety and stress.