Wismodegib — szansa na istotną poprawę jakości życia u chorych na miejscowo zaawansowanego raka podstawnokomórkowego skóry — opis przypadku

Rak podstawnokomórkowy jest najczęstszym nowotworem skóry. Obecnie dostępne strategie terapeutyczne obejmują leczenie chirurgiczne i radioterapię oraz — u chorych z niskim ryzykiem nawrotu — powierzchowne stosowanie preparatów fluorouracylu i imikwimodu. Rak podstawnokomórkowy jest często umiejscowiony na skórze okolicy gałki ocznej i nierzadko penetruje w głąb tkanek, a zastosowanie standardowych metod leczenia może prowadzić do ślepoty. Doustne małocząsteczkowe leki hamujące kluczowy dla rozwoju raka podstawno­komórkowego szlak Hedgehog stanowią nową opcję terapeutyczną u chorych w stadium zaawansowanym, którzy nie kwalifikują się do leczenia chirurgicznego lub radioterapii. Prezentowany przypadek dotyczy chorego na miejscowo zaawansowanego raka podstawnokomórkowego okolicy skóry twarzy oraz zatok i oczodołu, który był poddany rozległemu zabiegowi operacyjnemu z ewentracją prawej gałki ocznej. Po 8 miesiącach od zabiegu stwierdzono miejscowy nawrót choroby. Ze względu na rozległość zmian odstąpiono od zabiegu chirurgicznego. Zastosowanie radioterapii wiązałoby się z dużym ryzykiem ślepoty pozostałej gałki ocznej. U chorego wdrożono leczenie wismodegibem, które doprowadziło do uzyskania całkowitej odpowiedzi w wyniku zastosowanego leczenia. Ponadto uniknięto utraty wzroku, który zostałby uszkodzony w przebiegu radioterapii. Ustąpiły również objawy związane z miejscowym szerzeniem się nowotworu. Chory od 20 miesięcy przyjmuje inhibitor szlaku Hedgehog bez cech progresji w badaniach obrazowych

Miejsce chemioterapii w leczeniu chorych na zaawansowanego lub nawrotowego raka ślinianki

Since malignant tumors of salivary glands are heterogeneous and rare it is hardly possible to conduct randomizedclinical trials devoted to these malignancies. Therefore clinical data available in the literature come almost solelyfrom small retrospective clinical studies or case reports. Among several malignant tumors of salivary gland theadenoid cystic carcinoma is most frequently described and discussed in the literature. There are no formal recommendationsissued by oncologic societies on the systemic treatment of patients with advanced/metastaticsalivary gland malignancies. This article is aimed to summarize available data on systemic treatment of patientswith malignant salivary gland tumors with special interest in clinical efficacy of various chemotherapy regimensin particular tumor types.Duża różnorodność typów raków ślinianek oraz mała częstotliwość ich występowania utrudnia przeprowadzeniebadań klinicznych. W piśmiennictwie znajdujemy najczęściej retrospektywne opisy przypadków, nie prospektywnebadania kliniczne. Rak gruczołowo-torbielowaty jest typem histologicznym, który z tej rzadkiej grupy nowotworówwystępuje najczęściej w badanych populacjach.Do tej pory nie ustalono optymalnego schematu chemioterapii w przypadku miejscowo zaawansowanej/przerzutowejchoroby, która mogłaby wpłynąć na zmniejszenie objawów. Podejmowano próby zastosowania mono- i polichemioterapii.Potrzebna jest weryfikacja schematów leczenia, która pozwoliłaby określić najbardziej aktywne lekizarówno w przypadku raka gruczołowo-torbielowatego, jak i pozostałych typach histologicznych raków ślinianek

Biological role of long non-coding RNA in head and neck cancers

AimHead and neck squamous cell carcinoma (HNSCC) are one of the worst prognosis cancers with high mortality of patients. The treatment strategy is primarily based on surgery and radiotherapy but chemotherapy is also used. Every year the knowledge concerning HNSCC biology is updated with new elements such as the recent discovered molecules – long non-coding RNAs. Long non-coding RNAs are involved in regulatory processes in the cells. It has been revealed that the expression levels of lncRNAs are disturbed in tumor cells what results in the acquisition of their specific phenotype. lncRNAs influence cell growth, cell cycle, cell phenotype, migration and invasion ability as well as apoptosis. Development of the lncRNA panel characteristic for HNSCC and validation of specific lncRNA functions are yet to be elucidated. In this work, we collected available data concerning lncRNAs in HNSCC and characterized their biological role. We believe that the tumor examination, in the context of lncRNA expression, may lead to understanding complex biology of the cancer and improve therapeutic methods in the future

Wismodegib w leczeniu zaawansowanego raka podstawnokomórkowego skóry — polskie doświadczenia kliniczne w ramach programu lekowego

Wstęp. Wismodegib to małocząsteczkowy inhibitor szlaku sygnałowego Hedgehog zarejestrowany do leczenia pacjentów, u których stwierdzono raka podstawnokomórkowego w fazie choroby przerzutowej lub miejscowo zaawansowanego raka podstawnokomórkowego niespełniającego kryteriów leczenia chirurgicznego lub radiote- rapeutycznego. Od 1 stycznia 2017 roku dostępne jest na terenie Polski leczenie w ramach programu lekowego refundowanego przez NFZ.  Celem pracy była analiza grupy chorych zakwalifikowanych do terapii wismodegibem, uwzględniająca ocenę częstości występowania działań niepożądanych wraz z określeniem ich stopnia nasilenia według CTCAE oraz wyniki leczenia po 6 i 12 miesiącach zgodnie z kryteriami RECIST 1.1. Materiał i metody. Dane dotyczące chorych pochodziły z trzech ośrodków, które w sumie prowadziły 42/78 (53,8%) pacjentów leczonych w Polsce od początku trwania programu lekowego. Czas leczenia chorych był bardzo zróżnicowany i zawierał się pomiędzy 3 tygodniami a 68 miesiącami. Mediana czasu leczenia wyniosła 8,25 miesiąca (0,75–68), mediana czasu obserwacji pacjentów leczonych krócej lub dłużej niż 12 miesięcy — wyniosła odpowiednio 8 miesięcy (6–11) i 14 miesięcy (12–68).  Wyniki. Podsumowanie danych po 6 i 12 miesiącach leczenia było możliwe odpowiednio u 29/42 i 17/42 chorych. Całkowitą odpowiedź uzyskano u 3/29 (10,3%) oraz u 3/16 (17,6%) pacjentów po odpowiednio 6 i 12 miesiącach leczenia, częściową odpowiedź odnotowano odpowiednio u 13/29 (44,8%) i 5/16 (29,4%) pacjentów, stabilizację choroby uzyskano odpowiednio u 13/29 (44,8%) i 8/16 (50,0%). Progresję choroby stwierdzono u 7 z 42 chorych (16,6%) w okresie 3–28 miesięcy od rozpoczęcia leczenia. Odnotowano 1 przypadek zgonu z powodu progresji choroby u pacjenta z obecnymi przerzutami do mózgu w momencie kwalifikacji do udziału w programie. Działania niepożądane wystąpiły u 31/42 (73,8%), a liczne działania niepożądane u tego samego pacjenta wystąpiły u 22/42 (52,3%) chorych. Nie odnotowano żadnego przypadku poważnych działań niepożądanych

Vismodegib in the treatment of basal cell carcinoma — Polish clinical experience in the frame of therapeutic program

Introduction. Vismodegib is a small-molecule inhibitor of the sonic hedgehog pathway, registered for the treat- ment of patients with metastatic or locally advanced basal cell carcinoma, who were disqualified from surgical excision or radiotherapy. The full treatment refund from the National Health Fund has been available in Poland since 1st January 2018. The aim of the study was to analyse the frequency of occurrence of adverse events based on CTCAE and the treatment results based on the RECIST 1.1 criteria, in a group of patients treated for six or 12 months with vismodegib.  Material and methods. The patient database was gathered from three sites and consisted of 42 patients, who represented 53.8% of the patients treated with vismodegib in Poland. The duration of the treatment ranged between three weeks and 68 months. The median of the treatment period was 8.25 months (0.75–68); the median of the observation of patients treated for less than 12 months was eight months (6–11), and for those treated for more than 12 months it was 14 months (12–68).  Results. The summary of the treatment results after six and 12 months was performed on 29/42 and 17/42 patients accordingly. Complete response was achieved in 3/29 (10.3%) and 3/16 (17.6%) patients after six and 12 months of treatment, respectively, partial response in 13/29 (44.8%) and 5/16 (29.4%) patients, respectively, and stable disease in 13/29 (44.8%) and 8/16 (50.0%) patients, respectively. Progression of the disease was experienced by 7/42 (16.6%) patients within the period of 3–28 months of treatment. One patient with brain metastases died due to the progression of the disease. Adverse events were reported in 31/42 (73.8%) patients, more than one adverse event in a single patient was reported in 22/42 (52.3%) patients. No serious adverse events were observed.

The impact of antibiotics and glucocorticoids on the results of immunomodulatory antibody treatment in cancer patients

Cancer cells avoid elimination through the mechanism of immunosuppression, which consists in modulatingantigens and affecting the activation of the complement system. In 2011, authorities registereda monoclonal antibody and the first medication from the group of immunological checkpoints, ipilimumab,which activates T lymphocytes through unblocking the possibility of presenting antigens to cells afterbinding with cytotoxic T cell antigen (CTLA-4 ). Other targets of the drugs from this group were described:programmed death cell receptor 1 (PD-1), located on T lymphocytes, and programmed death cell ligand 1(PD-L1), located on cancer cells. Immunotherapy significantly improved the prognosis of patients diagnosedwith melanoma, renal cell carcinoma, squamous cell carcinomas of the head and neck, non-smallcell lung cancer and other cancers Glucocorticoids are often used in the treatment of symptoms in cancer patients. They are also administeredduring immunotherapy in the case of immune-related adverse events. Antibiotics also constitute a group ofmedications that are widely used in cancer patients. Since both glucocorticoids and antibiotics can decreasethe effectiveness of immunotherapy, physicians should carefully consider the expected benefits and the possiblenegative impact of their administration on the survival time of cancer patients before prescribing them.Cancer cells avoid elimination through the mechanism of immunosuppression, which consists in modulating antigens and affecting the activation of the complement system. In 2011, authorities registered a monoclonal antibody and the first medication from the group of immunological checkpoints, ipilimumab, which activates T lymphocytes through unblocking the possibility of presenting antigens to cells after binding with cytotoxic T cell antigen (CTLA-4 ). Other targets of the drugs from this group were described: programmed death cell receptor 1 (PD-1), located on T lymphocytes, and programmed death cell ligand 1 (PD-L1), located on cancer cells. Immunotherapy significantly improved the prognosis of patients diagnosed with melanoma, renal cell carcinoma, squamous cell carcinomas of the head and neck, non-small cell lung cancer and other cancers. Glucocorticoids are often used in the treatment of symptoms in cancer patients. They are also administered during immunotherapy in the case autoimmune complications. Antibiotics also constitute a group of medications that are widely used in cancer patients. Since both glucocorticoids and antibiotics can decrease the effectiveness of immunotherapy, physicians should carefully consider the expected benefits and the possible negative impact of their administration on the survival time of cancer patients before prescribing them

Vismodegib — a chance for improvement of quality of life in patients with locally advanced basal cell carcinoma — a case report

Basal cell carcinoma (BCC) is the most common non-melanocytic skin cancer. Therapeutic strategies available so far include: surgical resection, radiotherapy, or — in the case of low risk of recurrence — superficial application of drugs like 5-fluorouracil or imiquimod. The frequent localisation of BCC is eye bulb area, often with deep penetration into the tissues. Standard therapies in this area may lead to blindness. The Hedgehog (HH) pathway is a key point in BCC development. For patients with advanced BCC, not suitable for surgical resection or radiotherapy, oral small-molecule drug inhibitors of this pathway are the new therapeutic option. Here we present a case of a patient with locally advanced skin BCC localised on the face, sinuses, and eye-socket region. Wide excision with the right eye bulb resection was performed. Eight months after the treatment the patient developed regional recurrence. Due to the advanced stage of the disease the patient was disqualified from further surgical resection. Use of radiotherapy was associated with high risk of blindness of the left eye. The patient was treated with vismodegib and developed a complete response. Moreover, we avoided blindness after radiotherapy. Also, the patient’s symptoms due to locally spreading cancer resolved. The patient has been receiving HH inhibitor without any progression in imaging tests for 20 months

Perioperative treatment of oesophageal, oesophago-gastric and gastric adenocarcinoma: new standards of care and controversies

Oesophageal, gastroesophageal and gastric cancers represent important diagnostic and therapeutic challenge. Even after radical surgical procedure (R0) 5-year survival remains unsatisfactory. It is assumed that perioperative chemo/radiotherapy eliminates local and distant micrometastases. This year (2012) a consensus on the primary therapy of gastric, gastroesophageal and oesophageal cancer was published as a result of the first EORTC St. Gallen International Expert Consensus. Despite a significant progress in the perioperative treatment of locally advanced cancers of upper digestive tract, results of several ongoing clinical trials that may further optimize systemic treatment of these malignancies are eagerly awaited.Rak przełyku, połączenia przełykowo-żołądkowego oraz żołądka to duży problem diagnostyczny i terapeutyczny. Nawet po zabiegach chirurgicznych (R0) odsetek przeżyć 5-letnich jest niezadowalający. Chemioterapia okołooperacyjna czy chemioradioterapia uzupełniająca umożliwiają znamienną poprawę rokowania chorych, gdyż zmniejszają ryzyko nawrotu regionalnego oraz uogólnienia. W roku 2012 w St. Gallen odbyła się pierwsza konferencja uzgodnieniowa dotycząca leczenia okołooperacyjnego raka przełyku i żołądka. Pomimo znacznego postępu w tej dziedzinie z niecierpliwością oczekuje się na wyniki kolejnych badań klinicznych, które pozwolą na dalsze zoptymalizowanie dotychczasowych strategii terapeutycznych w tym rozpoznaniu

Basal Cell Carcinoma: Pathology, Current Clinical Treatment, and Potential Use of Lipid Nanoparticles

Skin cancer is the most common type of carcinoma diagnosed worldwide, with significant morbidity and mortality rates among Caucasians, in particular basal cell carcinoma (BCC). The main risk factors of BCC are well-identified, and there are many chemotherapeutic drugs available for its treatment. The effectiveness of therapeutic options is governed by several factors, including the location of the tumor, its size, and the presence of metastases (although rare for BCC). However, available treatments are based on non-targeted approaches, which encounter a significant risk of systemic toxicity in several organs. Site-specific chemotherapy for BCC has been proposed via the loading of anticancer drugs into nanoparticles. Among various types of nanoparticles, in this review, we focus on potential new regimens for the treatment of BCC using classical anticancer drugs loaded into novel lipid nanoparticles. To meet patient aesthetic expectations and enhance the effectiveness of basal cell carcinoma treatment, new therapeutic topical strategies are discussed, despite a limited number of reports available in the literature

lncRNA Expression after Irradiation and Chemoexposure of HNSCC Cell Lines

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world. To improve the quality of diagnostics and patients’ treatment, new and effective biomarkers are needed. Recent studies have shown that the expression level of different types of long non-coding RNAs (lncRNAs) is dysregulated in HNSCC and correlates with many biological processes. In this study, the response of lncRNAs in HNSCC cell lines after exposure to irradiation and cytotoxic drugs was examined. The SCC-040, SCC-25, FaDu, and Cal27 cell lines were treated with different radiation doses as well as exposed to cisplatin and doxorubicin. The expression changes of lncRNAs after exposure to these agents were checked by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target prediction was performed using available online tools and classified into specific biological processes and cellular pathways. The results indicated that the irradiation, as well as chemoexposure, causes changes in lncRNA expression and the effect depends on the cell line, type of agents as well as their dose. After irradiation using the dose of 5 Gy significant dysregulation of 4 lncRNAs, 10 Gy-5 lncRNAs, and 20 Gy-3 lncRNAs, respectively, were observed in all cell lines. Only lncRNAs Zfhx2as was down-regulated in all cell lines independently of the dose used. After cisplatin exposure, 14 lncRNAs showed lower and only two higher expressions. Doxorubicin resulted in lower expressions of eight and increased four of lncRNAs. Common effects of cytotoxic drugs were observed in the case of antiPEG11, BACE1AS, PCGEM1, and ST7OT. Analysis of the predicted targets for dysregulated lncRNAs indicated that they are involved in important biological processes, regulating cellular pathways connected with direct response to irradiation or chemoexposure, cellular phenotype, cancer initiating cells, and angiogenesis. Both irradiation and chemoexposure caused specific changes in lncRNAs expression. However, the common effect is potentially important for cellular response to the stress and survival. Further study will show if lncRNAs are useful tools in patients’ treatment monitoring