Selected articles
PI3K/Akt/mTOR signaling pathway and breast cancer – from molecular targets to clinical aspects
04/2021 Doc. MUDr. Jana Dvořáčková, Ph.D., MIAC; Mgr. Barbora Kubová; Mgr. Jarmila Šimová; RNDr. Magdalena Uvírová, Ph.D.
Breast cancer is one of the most common malignancies in women. The PI3K/Akt/mTOR signaling pathway plays an important role in several cellular processes involved in proliferation, metabolism, cell growth, and survival. Alterations in this signaling pathway have been found in a variety of tumors, including breast cancer. Constitutive activation of the PI3K/Akt/mTOR signaling pathway plays a key role in tumor pathogenesis and resistance to conventional therapy. In connection with the newly approved treatment with PI3K inhibitors, the determination of PIK3CA mutation status as a predictive marker is also gaining in importance.
ENTIRE ARTICLE
Breast cancer is one of the most common malignancies in women. The PI3K/Akt/mTOR signaling pathway plays an important role in several cellular processes involved in proliferation, metabolism, cell growth, and survival. Alterations in this signaling pathway have been found in a variety of tumors, including breast cancer. Constitutive activation of the PI3K/Akt/mTOR signaling pathway plays a key role in tumor pathogenesis and resistance to conventional therapy. In connection with the newly approved treatment with PI3K inhibitors, the determination of PIK3CA mutation status as a predictive marker is also gaining in importance.
Radiotherapy in the treatment of breast cancer
04/2021 MUDr. Tomáš Svoboda, Ph.D.; Bc. Daniela Čechová
Radiotherapy is one of the most basic methods of anticancer treatment, including breast cancer. It is used in a number of situations in terms of use, it is most often a standard part of adjuvant treatment, but it can be used at any time with a palliative intention, both in the area of primary tumor and metastatic disease in virtually any location. The method is undergoing huge development. Thanks to the use of modern diagnostic methods, planning has been significantly refined, fractionation regimes are undergoing development, and with much better instrumentation, much stricter limits can be applied to protect the surrounding organs. Radiation oncologists are able to respond to a wide range of situations, such as reconstructive procedures, adjustments of target volumes based on a comparison of risks against benefits, but also to replace previously common radical surgical procedures. Breast saving surgery and removal of only the sentinel node, in most cases supplemented by radiation therapy, represent a completely comparable alternative while maintaining the mental state, body integrity and quality of life of patients. On the contrary, studies based on the administration of systemic therapy in combination with radiotherapy with the omission of surgical treatment are currently underway. The results will certainly be interesting, but a relatively long follow up time will be needed to sufficiently compare the different approaches.
ENTIRE ARTICLE
Radiotherapy is one of the most basic methods of anticancer treatment, including breast cancer. It is used in a number of situations in terms of use, it is most often a standard part of adjuvant treatment, but it can be used at any time with a palliative intention, both in the area of primary tumor and metastatic disease in virtually any location. The method is undergoing huge development. Thanks to the use of modern diagnostic methods, planning has been significantly refined, fractionation regimes are undergoing development, and with much better instrumentation, much stricter limits can be applied to protect the surrounding organs. Radiation oncologists are able to respond to a wide range of situations, such as reconstructive procedures, adjustments of target volumes based on a comparison of risks against benefits, but also to replace previously common radical surgical procedures. Breast saving surgery and removal of only the sentinel node, in most cases supplemented by radiation therapy, represent a completely comparable alternative while maintaining the mental state, body integrity and quality of life of patients. On the contrary, studies based on the administration of systemic therapy in combination with radiotherapy with the omission of surgical treatment are currently underway. The results will certainly be interesting, but a relatively long follow up time will be needed to sufficiently compare the different approaches.
Triple negative breast cancer
04/2021 MUDr. Michaela Miškovičová, Ph.D.
Triple negative breast cancer (TNBC) represents a heterogeneous group of breast cancers, histologically, molecularly biologically and immunologically. A common molecular feature is that they do not express alpha estrogen, progesterone, and HER2 receptors.1 They appear to be the most aggressive subtype of breast cancer and are usually associated with a serious prognosis and increased mortality worldwide. Their extremely high proliferation and tendency to hematogenous metastasis are typical.2 The severity of this disease is primarily observed in younger women but can occur in all age groups. Epidemiologically, they represent about 15-20 % of newly diagnosed breast cancers.3 Young patients often suffer from worse clinical outcomes, such as early relapse and the appearance of visceral metastases. Current clinical treatment of TNBC is generally challenging, with chemoresistance and recurrent tumor recurrence being common barriers.4
We have seen little therapeutic progress in recent decades, and chemotherapy remains the standard of care. Although the incorporation of targeting agents such as poly (ADP ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors in clinical practice appears promising, TNBC responses to these therapies still vary widely. However, despite enriched chemosensitivity and immunogenicity, most patients with TNBC do not achieve satisfactory clinical responses. The lack of specific effective therapeutic targets is one of the key factors preventing a significant improvement in the effect of targeted treatment.5 Incorporating immunomolecular targets into combination and improving standard chemotherapy, especially in the early stages of the disease, may be key to unlocking the promising future of management of TNBC.4
ENTIRE ARTICLE
Triple negative breast cancer (TNBC) represents a heterogeneous group of breast cancers, histologically, molecularly biologically and immunologically. A common molecular feature is that they do not express alpha estrogen, progesterone, and HER2 receptors.1 They appear to be the most aggressive subtype of breast cancer and are usually associated with a serious prognosis and increased mortality worldwide. Their extremely high proliferation and tendency to hematogenous metastasis are typical.2 The severity of this disease is primarily observed in younger women but can occur in all age groups. Epidemiologically, they represent about 15-20 % of newly diagnosed breast cancers.3 Young patients often suffer from worse clinical outcomes, such as early relapse and the appearance of visceral metastases. Current clinical treatment of TNBC is generally challenging, with chemoresistance and recurrent tumor recurrence being common barriers.4
We have seen little therapeutic progress in recent decades, and chemotherapy remains the standard of care. Although the incorporation of targeting agents such as poly (ADP ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors in clinical practice appears promising, TNBC responses to these therapies still vary widely. However, despite enriched chemosensitivity and immunogenicity, most patients with TNBC do not achieve satisfactory clinical responses. The lack of specific effective therapeutic targets is one of the key factors preventing a significant improvement in the effect of targeted treatment.5 Incorporating immunomolecular targets into combination and improving standard chemotherapy, especially in the early stages of the disease, may be key to unlocking the promising future of management of TNBC.4
Inhibitors of the cycline‑dependent kinases 4/6 in the treatment of patients with breast cancer
04/2021 MUDr. Marta Krásenská
Hormone receptor positive breast cancers are characterized by the presence of receptors for estrogen and/or progesterone and represent up to 75 %. Endocrine therapy is effective in neoadjuvant and adjuvant setting and remains the basic treatment modality for advanced disease. Up to half of patients with metastatic disease develop resistance to endocrine therapy. In order to modify the development of resistance to endocrine therapy, inhibitors of the cyclin-dependent kinases 4/6 have been developed. Palbociclib, ribociclib and abemaciclib have shown statistically and clinically significant efficacy in many III phase clinical trials. Consistently, they almost double progression free survival, increase the overall response rates, and prolong patient survival. In combination with an aromatase inhibitor and fulvestrant, they have become the new standard for first and second line treatment of hormone receptor positive metastatic breast cancer.
ENTIRE ARTICLE
Hormone receptor positive breast cancers are characterized by the presence of receptors for estrogen and/or progesterone and represent up to 75 %. Endocrine therapy is effective in neoadjuvant and adjuvant setting and remains the basic treatment modality for advanced disease. Up to half of patients with metastatic disease develop resistance to endocrine therapy. In order to modify the development of resistance to endocrine therapy, inhibitors of the cyclin-dependent kinases 4/6 have been developed. Palbociclib, ribociclib and abemaciclib have shown statistically and clinically significant efficacy in many III phase clinical trials. Consistently, they almost double progression free survival, increase the overall response rates, and prolong patient survival. In combination with an aromatase inhibitor and fulvestrant, they have become the new standard for first and second line treatment of hormone receptor positive metastatic breast cancer.
Predictive markers in breast cancer
04/2021 MUDr. Zuzana Bielčiková, Ph.D.
Prognostic and predictive markers are the way to the treatment personalization. Prediction of prognosis is important for stratifying the disease according to the risk of relapse and is a prerequisite for escalation or de-escalation of treatment. In the case of early hormone-sensitive (HR+) breast cancer, multigene assays (MGA) in particular fulfil this role. There are also hopes for the prognostic significance of proliferation activity of the disease (Ki 67) in response to neoadjuvant hormonal therapy. For aggressive subtypes (human epidermal growth factor receptor 2 - positive [HER2+] and triple negative breast cancer [TNBC]), main prognostic markers are the achievement of pathological complete remission and the presence of tumor infiltrating lymphocytes, programmed death ligand 1 (PD L1) also stayed in this category. The only and already established predictive markers of therapy response in early breast cancer remain the estrogen receptor (ER) and HER2. We're slightly better at predicting of therapy response in metastatic breast cancer; to ER and HER2 we can add PD L1 in metastatic TNBC, a mutation in the PIK3CA gene in HR+ cancer, and the presence of mutations in BRCA genes as predictors for inhibitors of PARP Prediction of therapeutic effect is also a prerequisite for improving patient survival and for reducing the toxicity of non-target treatment.
ENTIRE ARTICLE
Prognostic and predictive markers are the way to the treatment personalization. Prediction of prognosis is important for stratifying the disease according to the risk of relapse and is a prerequisite for escalation or de-escalation of treatment. In the case of early hormone-sensitive (HR+) breast cancer, multigene assays (MGA) in particular fulfil this role. There are also hopes for the prognostic significance of proliferation activity of the disease (Ki 67) in response to neoadjuvant hormonal therapy. For aggressive subtypes (human epidermal growth factor receptor 2 - positive [HER2+] and triple negative breast cancer [TNBC]), main prognostic markers are the achievement of pathological complete remission and the presence of tumor infiltrating lymphocytes, programmed death ligand 1 (PD L1) also stayed in this category. The only and already established predictive markers of therapy response in early breast cancer remain the estrogen receptor (ER) and HER2. We're slightly better at predicting of therapy response in metastatic breast cancer; to ER and HER2 we can add PD L1 in metastatic TNBC, a mutation in the PIK3CA gene in HR+ cancer, and the presence of mutations in BRCA genes as predictors for inhibitors of PARP Prediction of therapeutic effect is also a prerequisite for improving patient survival and for reducing the toxicity of non-target treatment.
Long‑term treatment of metastatic urothelial carcinoma of the renal pelvis – case report
03/2021 MUDr. Michaela Barjaková; MUDr. Robert Novák; MUDr. Jana Katolická, Ph.D.; doc. MUDr. Jiří Vaniček, Ph.D.
Urothelial tumors of the upper urinary tract make up only about 5% of the urothelial tumors. In the treatment of metastatic disease, we use chemotherapeutic regimens based on a platinum derivative, as in urothelial bladder cancer. Following failure of a platinum derivative, vinflunine or taxanes (especially paclitaxel) may be given from chemotherapy in case of good performance status.
ENTIRE ARTICLE
Urothelial tumors of the upper urinary tract make up only about 5% of the urothelial tumors. In the treatment of metastatic disease, we use chemotherapeutic regimens based on a platinum derivative, as in urothelial bladder cancer. Following failure of a platinum derivative, vinflunine or taxanes (especially paclitaxel) may be given from chemotherapy in case of good performance status.
Treatment of metastatic colorectal cancer in a 44‑year‑old woman with internal comorbidities – a case report
03/2021 MUDr. Věra Benešová
In this case report, I describe the course of treatment of metastatic colorectal cancer in a 44-year-old woman with type 1 diabetes mellitus with insulin therapy and hypertension. The decision on the treatment sequence respected the current recommendations for the treatment of metastatic colorectal cancer, namely: examination in a multidisciplinary team, determination of the genetic type of the tumor, placement of the tumor and the overall lineage of the patient. Because the tumor was KRAS, NRAS wild-type, multiple liver lesions have been found in both lobes and it was left-sided cancer, systemic chemotherapy FOLFOX6 in combination with an epidermal growth factor receptor inhibitor, panitumumab (Vectibix inj.), has been chosen.
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In this case report, I describe the course of treatment of metastatic colorectal cancer in a 44-year-old woman with type 1 diabetes mellitus with insulin therapy and hypertension. The decision on the treatment sequence respected the current recommendations for the treatment of metastatic colorectal cancer, namely: examination in a multidisciplinary team, determination of the genetic type of the tumor, placement of the tumor and the overall lineage of the patient. Because the tumor was KRAS, NRAS wild-type, multiple liver lesions have been found in both lobes and it was left-sided cancer, systemic chemotherapy FOLFOX6 in combination with an epidermal growth factor receptor inhibitor, panitumumab (Vectibix inj.), has been chosen.
Treatment of ALK positive non‑small cell lung cancer
03/2021 MUDr. Markéta Černovská
Anaplastic lymphoma kinase (ALK) mutations were first described in non-small cell lung cancer (NSCLC) in 2007. ALK inhibitors are anti-cancer drugs that act on tumours with variations of ALK such as an EML4-ALK translocation. ALK inhibitors have shown significant benefits in the management of ALK-positive NSCLC compared to conventional chemotherapy. Crizotinib was the first ALK inhibitor which compared to standard chemotherapy prolonged progression-free survival. However, many patients with ALK-positive experience clinical progression and frequent brain metastases in the first year of treatment with crizotinib during the poor accumulation of the drug in the central nervous system (CNS). Second-generation (alectinib, ceritinib, brigatinib) and the third-generation ALK inhibitors (lorlatinib), have increased potency and higher CNS activity compared to the first-generation crizotinib. A sequencing of ALK inhibitors in ALK-positive NSCLC prolonged an overall survival.
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Anaplastic lymphoma kinase (ALK) mutations were first described in non-small cell lung cancer (NSCLC) in 2007. ALK inhibitors are anti-cancer drugs that act on tumours with variations of ALK such as an EML4-ALK translocation. ALK inhibitors have shown significant benefits in the management of ALK-positive NSCLC compared to conventional chemotherapy. Crizotinib was the first ALK inhibitor which compared to standard chemotherapy prolonged progression-free survival. However, many patients with ALK-positive experience clinical progression and frequent brain metastases in the first year of treatment with crizotinib during the poor accumulation of the drug in the central nervous system (CNS). Second-generation (alectinib, ceritinib, brigatinib) and the third-generation ALK inhibitors (lorlatinib), have increased potency and higher CNS activity compared to the first-generation crizotinib. A sequencing of ALK inhibitors in ALK-positive NSCLC prolonged an overall survival.
The role of elotuzumab in the treatment of multiple myeloma
03/2021 Prof. MUDr. Ivan Špička, CSc.
Therapy of multiple myeloma has substantially changed during last two decades due to new generation biological drugs proteasome inhibitors, immunomodulators and monoclonal antibodies. Elotuzumab is first in class monoclonal antibody approved for clinical use by Food and Drug Administration as „breakthrough therapy". Its target antigen is surface receptor SLAMF7 (or CS1) from CD2 group and SLAMF (signaling lymphocytic activation molecule) family. At present elotuzumab is approved for relapsed myeloma patients in combination with dexamethasone and either lenalidomide or pomalidomide.
ENTIRE ARTICLE
Therapy of multiple myeloma has substantially changed during last two decades due to new generation biological drugs proteasome inhibitors, immunomodulators and monoclonal antibodies. Elotuzumab is first in class monoclonal antibody approved for clinical use by Food and Drug Administration as „breakthrough therapy". Its target antigen is surface receptor SLAMF7 (or CS1) from CD2 group and SLAMF (signaling lymphocytic activation molecule) family. At present elotuzumab is approved for relapsed myeloma patients in combination with dexamethasone and either lenalidomide or pomalidomide.
Pembrolizumab in the adjuvant treatment of melanoma
03/2021 MUDr. Eugen Kubala
Adjuvant therapy is considered the standard approach to the treatment of patients with locally advanced stage IIIA, IIIB and IIIC melanoma. The EORTC 1325-MG/KEYNOTE-045 study, which compared pembrolizumab with placebo, clearly demonstrated its efficacy. Long-term follow-up showed that 3-year relapse free survival (RFS) was achieved in 63.7 patients with pembrolizumab versus 44.1% in placebo patients (HR 0.56; 95% CI, 0.47-0.68; p < 0.001). This treatment has been shown to be highly safe with a low incidence of side effects. At the same time, the incidence of immunotherapy-related adverse events has been shown to be associated with better treatment outcomes than without them, especially in endocrine toxicity (p = 0.03). However, the absence of immunotherapy-related adverse events does not lead to a significant reduction in the efficacy of pembrolizumab over placebo.
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Adjuvant therapy is considered the standard approach to the treatment of patients with locally advanced stage IIIA, IIIB and IIIC melanoma. The EORTC 1325-MG/KEYNOTE-045 study, which compared pembrolizumab with placebo, clearly demonstrated its efficacy. Long-term follow-up showed that 3-year relapse free survival (RFS) was achieved in 63.7 patients with pembrolizumab versus 44.1% in placebo patients (HR 0.56; 95% CI, 0.47-0.68; p < 0.001). This treatment has been shown to be highly safe with a low incidence of side effects. At the same time, the incidence of immunotherapy-related adverse events has been shown to be associated with better treatment outcomes than without them, especially in endocrine toxicity (p = 0.03). However, the absence of immunotherapy-related adverse events does not lead to a significant reduction in the efficacy of pembrolizumab over placebo.
News in the systemic treatment of esophageal tumors
03/2021 Doc. MUDr. David Vrána, Ph.D.
Immunotherapy found its firm role in the treatment of several tumor types. Based on the recently pub- lished clinical trials immunotherapy got into treatment algorithm of esophageal and gastroesophageal cancer in the first line and also in later treatment lines. Predictive markers, which play a role in the treatment selection are programmed cell death-ligand 1 (PD-L1), deficient mismatch repair genes and high microsatellite instability (dMMR/MSI-H) and human epidermal growth factor receptor 2 (HER2) expression. Targeted therapy with trastuzumab, ramucirumab or therapy with trifluridine/tipiracil remains the treatment of choice in the case of gastroesophageal cancer. Unfortunately, the reimbursement by the health care insurance is missing so far for any immunotherapy molecule. Bellow mentioned text aims to summarize current data for immunotherapy, targeted therapy in the treatment of the esophageal and gastroesophageal cancer regardless of the insurance reimbursement.
ENTIRE ARTICLE
Immunotherapy found its firm role in the treatment of several tumor types. Based on the recently pub- lished clinical trials immunotherapy got into treatment algorithm of esophageal and gastroesophageal cancer in the first line and also in later treatment lines. Predictive markers, which play a role in the treatment selection are programmed cell death-ligand 1 (PD-L1), deficient mismatch repair genes and high microsatellite instability (dMMR/MSI-H) and human epidermal growth factor receptor 2 (HER2) expression. Targeted therapy with trastuzumab, ramucirumab or therapy with trifluridine/tipiracil remains the treatment of choice in the case of gastroesophageal cancer. Unfortunately, the reimbursement by the health care insurance is missing so far for any immunotherapy molecule. Bellow mentioned text aims to summarize current data for immunotherapy, targeted therapy in the treatment of the esophageal and gastroesophageal cancer regardless of the insurance reimbursement.
Anti‑EGFR treatment of colorectal cancer
03/2021 MUDr. Stanislav Batko
Treatment of metastatic colorectal cancer is based on the combination of chemotherapy and targeted therapy, in which anti-EGFR monoclonal antibodies cetuximab and panitumumab play a very important role in RAS + BRAF wild-type subgroup of patients. They have showed prolonged progression-free survival throughout all lines, with prolongation of overall survival demonstrated in first- and third-line studies. The most significant benefit in overall survival can be observed, when they are used in chemonaive metastatic colorectal cancer. In this setting anti-EGFR (epidermal growth factor receptor) therapies pro- vide deep and durable response. This effect of tumor mass reduction simultaneously allows a significant proportion of patients to achieve conversion and secondary resection of metastases associated with longer survival and potential for curability. In addition to the most commonly used doublets FOLFOX and FOLFIRI, panitumumab can be used in combination with 5-fluorouracil and leucovorin in elderly patients while maintaining its efficacy. At the same time, there is increasing experience with the use of anti-EGFR therapies in combination with the FOLFOXIRI triplet, demonstrating high potential to achieve resectability. The indication criteria have been newly expanded to include BRAF V600E mutated pre- treated metastatic colorectal cancer, where the combination of cetuximab with encorafenib resulted in a significant prolongation of overall survival.
ENTIRE ARTICLE
Treatment of metastatic colorectal cancer is based on the combination of chemotherapy and targeted therapy, in which anti-EGFR monoclonal antibodies cetuximab and panitumumab play a very important role in RAS + BRAF wild-type subgroup of patients. They have showed prolonged progression-free survival throughout all lines, with prolongation of overall survival demonstrated in first- and third-line studies. The most significant benefit in overall survival can be observed, when they are used in chemonaive metastatic colorectal cancer. In this setting anti-EGFR (epidermal growth factor receptor) therapies pro- vide deep and durable response. This effect of tumor mass reduction simultaneously allows a significant proportion of patients to achieve conversion and secondary resection of metastases associated with longer survival and potential for curability. In addition to the most commonly used doublets FOLFOX and FOLFIRI, panitumumab can be used in combination with 5-fluorouracil and leucovorin in elderly patients while maintaining its efficacy. At the same time, there is increasing experience with the use of anti-EGFR therapies in combination with the FOLFOXIRI triplet, demonstrating high potential to achieve resectability. The indication criteria have been newly expanded to include BRAF V600E mutated pre- treated metastatic colorectal cancer, where the combination of cetuximab with encorafenib resulted in a significant prolongation of overall survival.
Pancreatic cancer – current treatment options
03/2021 MUDr. Marián Liberko; doc. MUDr. Renata Soumarová, Ph.D., MBA
Pancreatic cancer represents disease with the worst long-term survival across all malignancies. In clinical practice, due to asymptomatic or non-specific signs and symptoms we diagnose patients mainly with locally advanced and metastatic disease, where median survival is approximately one year. Nevertheless, even in early stages after curative surgery we observe early local recurrence, or distant metastases and long-term survival is an exception even in early stages of disease. Nevertheless, in the last few years there is an improvement in median overall survival also in patients with pancreatic cancer. It is due to advancements in diagnostics, surgery, but mainly due to improvements in cancer treatment (chemotherapy - adjuvant, neoadjuvant, perioperative, induction and palliative, and also radiotherapy). There were published results of many studies across all stages (resectable, borderline resectable, locally advanced, metastatic) which showed improved survival. The aim of this article is to provide overview of current treatment options for pancreatic ductal adenocarcinoma.
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Pancreatic cancer represents disease with the worst long-term survival across all malignancies. In clinical practice, due to asymptomatic or non-specific signs and symptoms we diagnose patients mainly with locally advanced and metastatic disease, where median survival is approximately one year. Nevertheless, even in early stages after curative surgery we observe early local recurrence, or distant metastases and long-term survival is an exception even in early stages of disease. Nevertheless, in the last few years there is an improvement in median overall survival also in patients with pancreatic cancer. It is due to advancements in diagnostics, surgery, but mainly due to improvements in cancer treatment (chemotherapy - adjuvant, neoadjuvant, perioperative, induction and palliative, and also radiotherapy). There were published results of many studies across all stages (resectable, borderline resectable, locally advanced, metastatic) which showed improved survival. The aim of this article is to provide overview of current treatment options for pancreatic ductal adenocarcinoma.
Advanced hepatocellular carcinoma and successfully targeted the first‑line treatment with atezolizumab and bevacizumab according to IMbrave150 trial
03/2021 Prof. MUDr. Samuel Vokurka, Ph.D.
Hepatocellular carcinoma is a prognostically unfavorable malignancy with very limited possibilities to influence its course, especially in advanced stages of the disease. Treatment with atezolizumab and bevacizumab in the IMbrave150 study showed a significant prolongation of median progression and overall survival of 19,2 versus 13,4 months in sorafenib group of patients (HR 0,66; p = 0,0009). This has been the longest survival observed in the first-line phase III study in advanced hepatocellular carcinoma, so far.
ENTIRE ARTICLE
Hepatocellular carcinoma is a prognostically unfavorable malignancy with very limited possibilities to influence its course, especially in advanced stages of the disease. Treatment with atezolizumab and bevacizumab in the IMbrave150 study showed a significant prolongation of median progression and overall survival of 19,2 versus 13,4 months in sorafenib group of patients (HR 0,66; p = 0,0009). This has been the longest survival observed in the first-line phase III study in advanced hepatocellular carcinoma, so far.
Possibilities and substantiation of re‑treatment with anti‑EGFR drugs for pre‑treated RAS wild‑type advanced colorectal cancers
03/2021 MUDr. Zdeněk Linke
Initial failure of epidermal growth factor receptor (EGFR) inhibitor therapy in advanced RAS wild-type (wt) colorectal cancers may not necessarily mean its permanent and definitive ineffectiveness. It is possible to re-apply anti-EGFR treatment after previous disease progression (rechallenge), or after a previous interruption for reasons other than progression (reintroduction), or sequence, resp. rotation between two different EGFR blockers (sequence) or an attempt to overcome the resistance of anti-EGFR treatment by increasing its dose (escalation) or the possibility of continuous EGFR blockade. Clinical data are available to demonstrate that, especially after discontinuation of primary anti-EGFR therapy and subsequent differential therapy, sensitivity to this therapy does return. This is by changing the proportion of EGFR positive RAS wt tumor cells. This occurs during another, intervening therapy, which is based on an effect different from EGFR blockade. However, a prerequisite for the effect of reintroduced anti-EGFR treatment is its effectiveness during its previous, primary application.
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Initial failure of epidermal growth factor receptor (EGFR) inhibitor therapy in advanced RAS wild-type (wt) colorectal cancers may not necessarily mean its permanent and definitive ineffectiveness. It is possible to re-apply anti-EGFR treatment after previous disease progression (rechallenge), or after a previous interruption for reasons other than progression (reintroduction), or sequence, resp. rotation between two different EGFR blockers (sequence) or an attempt to overcome the resistance of anti-EGFR treatment by increasing its dose (escalation) or the possibility of continuous EGFR blockade. Clinical data are available to demonstrate that, especially after discontinuation of primary anti-EGFR therapy and subsequent differential therapy, sensitivity to this therapy does return. This is by changing the proportion of EGFR positive RAS wt tumor cells. This occurs during another, intervening therapy, which is based on an effect different from EGFR blockade. However, a prerequisite for the effect of reintroduced anti-EGFR treatment is its effectiveness during its previous, primary application.
Immunotherapy in the treatment of tumors of the esophagus, gastroesophageal junction and stomach
03/2021 MUDr. Lenka Ostřížková; MUDr. Ivana Kosíková
Tumors of the esophagus, gastroesophageal junction (GEJ) and stomach are the sixth other cause of death. The highest incidence and mortality are in Asia and southern and eastern Africa. However, even in the Czech Republic, the incidence and mortality have an upward trend. In more than half of the patients, the diagnosis is made in the primarily advanced or disseminated stage. Histologically, tumors have squamous cell carcinomas, which mainly affect the proximal two-thirds, and adenocarcinomas, which affect the distal third and the GEJ region. There are more adenocarcinomas in gastric tumors at the same time. Squamous cell carcinomas of the esophagus are predominantly found in the countries of Eastern Europe and Asia. Adenocarcinomas dominate in North America and Western Europe. Anatomical localization, histological type of tumor, evaluation, and extent of the disease (TNM classification) are the cornerstones for determining strategic therapy. Treatment is interdisciplinary and should be conducted through multidisciplinary teams. According to the results of clinical studies, new immunotherapeutic strategies, antibodies against cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and antibodies against programmed cell death protein 1 (PD-1) / programmed cell death-ligand 1 (PD-L1) also have their place in the treatment algorithm of esophageal and gastric tumors. The results of clinical studies have shown that the combination of immunotherapy and chemotherapy improves overall survival and prolongation of time to disease progression compared to chemotherapy alone. Both in the treatment of metastatic disease and in adjuvant administration.
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Tumors of the esophagus, gastroesophageal junction (GEJ) and stomach are the sixth other cause of death. The highest incidence and mortality are in Asia and southern and eastern Africa. However, even in the Czech Republic, the incidence and mortality have an upward trend. In more than half of the patients, the diagnosis is made in the primarily advanced or disseminated stage. Histologically, tumors have squamous cell carcinomas, which mainly affect the proximal two-thirds, and adenocarcinomas, which affect the distal third and the GEJ region. There are more adenocarcinomas in gastric tumors at the same time. Squamous cell carcinomas of the esophagus are predominantly found in the countries of Eastern Europe and Asia. Adenocarcinomas dominate in North America and Western Europe. Anatomical localization, histological type of tumor, evaluation, and extent of the disease (TNM classification) are the cornerstones for determining strategic therapy. Treatment is interdisciplinary and should be conducted through multidisciplinary teams. According to the results of clinical studies, new immunotherapeutic strategies, antibodies against cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and antibodies against programmed cell death protein 1 (PD-1) / programmed cell death-ligand 1 (PD-L1) also have their place in the treatment algorithm of esophageal and gastric tumors. The results of clinical studies have shown that the combination of immunotherapy and chemotherapy improves overall survival and prolongation of time to disease progression compared to chemotherapy alone. Both in the treatment of metastatic disease and in adjuvant administration.
Chemoembolization of primary and secondary liver tumors
03/2021 MUDr. Jan Zavadil; MUDr. Tomáš Rohan; MUDr. Matej Straka; MUDr. Lenka Ostřížková; MUDr. Tomáš Andrašina, Ph.D., MBA
Transarterial chemoembolization is an integral part of the treatment of intermediate primary and secondary liver tumors. Over the decades, this method has been constantly improved both in terms of technology and the possibilities of embolizing agents used and improves the prognosis of patients who often cannot undergo other therapies. This review article introduces the readers to the basic cha- racteristics of the performance itself, indications, methods, complications, and side effects. Finally, the success of the performances themselves is presented.
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Transarterial chemoembolization is an integral part of the treatment of intermediate primary and secondary liver tumors. Over the decades, this method has been constantly improved both in terms of technology and the possibilities of embolizing agents used and improves the prognosis of patients who often cannot undergo other therapies. This review article introduces the readers to the basic cha- racteristics of the performance itself, indications, methods, complications, and side effects. Finally, the success of the performances themselves is presented.
Metallic stent application in palliative treatment of malignant esophageal stenoses
03/2021 MUDr. Peter Matkulčík; MUDr. Tomáš Rohan; MUDr. Pavlína Slováková; MUDr. Tomáš Andrašina, Ph.D., MBA
Increasing incidence of esophageal malignancies led authors to publish this review article regarding possibilities of cooperation between oncologists and interventional radiologists. In this article we summarize up-to-date information about indications and contraindications of different types of stents and their complications. Article is also supplemented with our experience in department of non-vascular interventions at Department of Radiology and Nuclear Medicine of Faculty Hospital Brno and Faculty of Medicine of Masaryk University.
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Increasing incidence of esophageal malignancies led authors to publish this review article regarding possibilities of cooperation between oncologists and interventional radiologists. In this article we summarize up-to-date information about indications and contraindications of different types of stents and their complications. Article is also supplemented with our experience in department of non-vascular interventions at Department of Radiology and Nuclear Medicine of Faculty Hospital Brno and Faculty of Medicine of Masaryk University.
Prognostic markers for survival in patients with pancreatic ductal adenocarcinoma
03/2021 MUDr. Michal Eiď; MUDr. Štěpan Tuček, Ph.D.; MUDr. Lumír Kunovský, Ph.D.
Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing, and mortality remains high. It has already been proven that PDAC is not one uniform disease. It is considered a very heterogeneous malignancy. Despite a growing knowledge, no breakthrough therapy leading to long-term survival has been implemented into the clinical practice during last 30 years. An exception is an intensive triplet chemotherapy regimen with 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRINOX), that leads to median overall survival 54,4 months and median disease free survival 21,6 months in adjuvant setting. It should be noted that in this PRODIGE 24 trial, inclusion criteria were strict and study population was selected. This intensive chemotherapy regimen is not feasible for majority of patients in real clinical practice. However, there is a subpopulation of patients with PDAC who long-term survivors are. Several clinical markers helping to predict patienťs prognosis are already available. Recently, number of molecular prognostic markers were described, and they will probably have an important role in future. In this article we will discuss the clinical, histopathological, and molecular prognostic markers that can be useful for the prognostic stratification.
ENTIRE ARTICLE
Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing, and mortality remains high. It has already been proven that PDAC is not one uniform disease. It is considered a very heterogeneous malignancy. Despite a growing knowledge, no breakthrough therapy leading to long-term survival has been implemented into the clinical practice during last 30 years. An exception is an intensive triplet chemotherapy regimen with 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRINOX), that leads to median overall survival 54,4 months and median disease free survival 21,6 months in adjuvant setting. It should be noted that in this PRODIGE 24 trial, inclusion criteria were strict and study population was selected. This intensive chemotherapy regimen is not feasible for majority of patients in real clinical practice. However, there is a subpopulation of patients with PDAC who long-term survivors are. Several clinical markers helping to predict patienťs prognosis are already available. Recently, number of molecular prognostic markers were described, and they will probably have an important role in future. In this article we will discuss the clinical, histopathological, and molecular prognostic markers that can be useful for the prognostic stratification.
ARTA treatment of metastatic castration‑resistant prostate cancer – case report
02/2021 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Vladimír Šámal, Ph.D.; MUDr. Jiří Bartoš, MBA
The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has rapidly evolved over the past 10 years. The addition chemotherapy (docetaxel, cabazitaxel), androgen receptor targeted agents (ARTA - abiraterone, enzalutamide) and radium 223 has improved outcomes for patients with mCRPC. Abiraterone in our clinical practice is applied most often before the docetaxel-based chemotherapy. We present a case study of patient with mCRPC treated by abirateron (before chemotherapy) for four years.
ENTIRE ARTICLE
The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has rapidly evolved over the past 10 years. The addition chemotherapy (docetaxel, cabazitaxel), androgen receptor targeted agents (ARTA - abiraterone, enzalutamide) and radium 223 has improved outcomes for patients with mCRPC. Abiraterone in our clinical practice is applied most often before the docetaxel-based chemotherapy. We present a case study of patient with mCRPC treated by abirateron (before chemotherapy) for four years.