Recent developments have revealed various decisive discoveries in individualized oncology for many different entities—the individualization of treatment based on molecular markers representing just one of those milestones. The implication of epidermal growth factor receptor (EGFR) mutations for EGFR-tyrosine kinase inhibitor (TKI) treatment, the definition of the HER2 status in breast cancer and the application of the KRAS mutation analysis in colorectal cancer are examples for this development. All these activities have also been the major focus at the Cancer Research Institute in St. Petersburg, where I worked for many years. Within the last years, a growing connection between basic research activities and clinical application can be observed.
The American Society of Clinical Oncology (ASCO) held its annual meeting in Chicago, Illinois (USA) from June 1–5, 2012. In the lung cancer track, several hundreds of abstracts were presented. The following article will give an overview on some interesting and relevant abstracts. Beside new drugs, the role of biomarker, and maintenance therapy, we will also discuss issues on early-stage disease.
Primary angiosarcoma (PAS) of the breast that has not received any previous radiotherapy is a rare and highly aggressive tumor with the diagnostic pitfall of a high histological differentiation. Surgical resection is the primary treatment for these tumors. Wide excision of the tumor or mastectomy is the gold standard of treatment, but there is a high risk for locoregional and distant recurrences. Here we present a case of a 47-year-old premenopausal woman with PAS of the breast masquerading as hemangioma on the first core biopsy. One month after wide excision of the tumor, local recurrence occurred and another 3 months later disseminated metastases were diagnosed in the lungs and in the spine of the patient.
The treatment of gastrointestinal cancer involves many medical disciplines, and several novel strategies and drugs are currently the subject of clinical studies. The most relevant results on studies in gastrointestinal cancer as presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO) are reviewed here.
We present the case of a 58-year-old woman referred to our outpatient department because of the elevated serum levels of carcinoembryonic antigen (CEA) during routine follow-up 6 years after the diagnosis and therapy of localized rectal cancer. Radiographic and endoscopic examinations did not reveal tumor recurrence or metastases. An asymptomatic hypothyroidism was diagnosed by routine serum marker analysis. Serum CEA level decreased upon adequate substitution of the hypothyroidism. This case illustrates the influence of thyroid function on Serum CEA levels and confirms hypothyroidism as a rare but relevant differential diagnosis of elevated serum CEA levels.
We describe the case of a 55-year-old woman initially diagnosed with locally advanced rectal cancer and one synchronous hepatic metastasis in 1998 who was treated by neoadjuvant chemotherapy and chemoradiotherapy followed by resection of the rectum and simultaneous atypical liver resection. After complete remission for about 4 years, the patient metachronously developed two local relapses and a liver metastasis, which were curatively treated by means of either radical resection or local ablative therapies and chemotherapy. Since the patient has refused radical resection of pulmonary metastases in November 2010, she is under palliative chemotherapy and is still alive. This case illustrates that a multimodality treatment can provide long-term survival in patients with metastasized colorectal cancer.
Allogeneic stem cell transplantation (SCT) had traditionally been the first-line therapy of chronic myeloid leukaemia (CML), but the introduction of tyrosine kinase inhibitors (TKI) has caused a major change to the treatment algorithm. The majority of patients in chronic phase obtain an excellent response to these oral agents with minimal toxicity. SCT is therefore used only in a minority of patients who do not achieve adequate response to first-, second- or even third-generation agents. Patients in accelerated phase are less likely to achieve an optimal response and for patients in blast phase, SCT continues to be the only therapy with curative potential although it is now increasingly used in combination with TKI. This review discusses the place of SCT in the current therapy of CML.
Bronchus-associated Lymphoid Tissue (BALT) lymphoma is a rare type of extranodal marginal zone lymphoma. It is defined as subgroup of B-cell non-Hodgkin’s lymphoma typically with an indolent clinical course. Often the clinical symptoms of pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas are highly heterogeneous with more than half of the patients initially suffering from multiple manifestations. Due to the rarity of this tumour and lack of randomized data, the optimal therapeutical pathway remains controversial. We report a case of this rare tumour with characteristic histological features. The patient complained about severe hemoptysis caused by an isolated tracheobronchial manifestation. According to treatment recommendations of extranodal MALT lymphomas, curative radiotherapy was administered, resulting in a complete and sustaining tumour remission and relief of symptoms.
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive brain tumor with an unsatisfactory prognosis. This is probably caused by the little knowledge of the biology and the molecular mechanisms of the disease with a consequent lacking of new targeted therapies and by the poor clinical conditions and performance status of patients, rendering their enrollment in prospective trials very difficult. Chemotherapy followed by radiotherapy is the most commonly used strategy for patients with PCNSL, which is not only associated with better efficacy rates, but also with high incidence of severe neurotoxicity. A relevant dilemma in PCNSL treatment regards the choice between strategies designed to intensify therapy to improve the cure rate, versus strategies of treatment deescalation to avoid severe neurotoxicity. The efficacy of chemotherapy is strongly limited by the special functional and microenvironmental characteristics of the central nervous system (CNS), which is variably protected by the blood–brain barrier (BBB) and includes extensive chemotherapy sanctuaries where tumor cells grow undisturbed. Methotrexate plus cytarabine combination is the current standard chemotherapeutic approach for newly diagnosed PCNSL, since it is supported by a recently published randomized trial. Other strategies are based on the use of other chemotherapy agents (temozolomide, topotecan, and thiotepa) and monoclonal antibodies (rituximab). Consolidation after chemotherapy represents the best role for radiotherapy. Some authorities are investigating in randomized trials which impact on outcome and neurotolerability of replacing consolidation radiotherapy with other strategies such as high-dose chemotherapy (HDC) supported by autologous stem cell transplantation (ASCT).
Zimmermann, Claudia; Pötschger, Ulrike; Amann, Gabriele; Horcher, Ernst; Dieckmann, Karin; Lakatos, Karoly; Urban, Christian; Lackner, Herwig; Höllwarth, Michael; Meister, Bernhard; Crazzolara, Roman; Ebetsberger, Georg; Fink, Franz Martin; Jones, Neil; Gamper, Agnes; Moser, Reinhard; Kerbl, Reinhold; Jauk, Barbara; Pobegen, Walter; Henkel, Martin; Ausserer, Bernd; Friesenbichler, Waltraud; Böhm, Judith; Graf, Norbert; Holter, Wolfgang; Gadner, Helmut; Zoubek, Andreas; Kager, Leo
The overall outcome for children with nephroblastomas is excellent when treated according to protocols that include surgery, chemotherapy, and, in selected cases, radiotherapy. This study was conducted to provide population-based data on Austrian children who had been treated in neoadjuvant nephroblastoma trials between October 1988 and July 2001. One hundred and forty-eight children with newly diagnosed untreated renal tumors were registered in the Austrian–Hungarian Wilms Tumor Study (AHWTS) 1989 (N = 63) and the SIOP 93-01/GPOH Study (N = 85). After a median follow-up of 11.8 years from diagnosis, 130 patients have been reported to be alive; 18 patients have died. Three patients had carcinoma and three had nephroblastomatosis; the 5-year event-free survival (EFS) and overall survival (OS) rates for the remaining 142 patients were 83 ± 3 % and 91 ± 2 %, respectively (SIOP 93-01/GPOH trial, 5-year EFS 85 ± 4 %, OS 95 ± 2 %; AHWTS 1989 trial, 5-year EFS 79 ± 5 %, OS 86 ± 5 %). Outcome was better for low-risk pathology (N = 14; 5-year EFS 92 ± 8 %, OS 100 %) than for intermediate-risk (N = 106; 5-year EFS 89 ± 3 %, OS 94 ± 2 %) and high-risk pathology (N = 22; 5-year EFS 50 ± 11 %, OS 68 ± 10 %; P < 0.001). The stage of the disease was correlated with outcome; stages I–III (N = 102; 5-year EFS 90 ± 3 %, OS 95 ± 2 %), stage IV (N = 25; 5-year EFS 56 ± 10 %, OS 76 ± 9 %), and stage V (N = 15; 5-year EFS 80 ± 10 %, OS 87 ± 9 %; P = 0.008). On the basis of the expected incidence for renal tumors in childhood, these data provide evidence that almost all children with these diseases in Austria had been recruited in the respective treatment trials (mean: 12 patients/year); and the outcomes are comparable to international results.
In the past few decades, many advances have been witnessed in the development of personalized molecular therapies, especially in the areas of melanoma and nonsmall cell lung cancer (NSCLC) among all other medical oncology fields. These therapies can be roughly divided into three categories at present: (1) targeting membrane-bound receptor tyrosine kinase (RTK), using either monoclonal antibodies or tyrosine kinase inhibitor (TKI), (2) targeting intracellular mitogen-activated protein kinase (MAPK) pathway, and (3) targeting intracellular phosphoinositide 3-kinase (PI3K) pathway. Currently, melanoma research focuses on MAPK pathway, spending efforts to clarify the intricate interactions in RAS–MEK–ERK-signaling cascades, whereas in the field of NSCLC, most achievements have been made targeting RTKs. This review will discuss the recent movements of drug development in these two areas, specifically BRAF and MEK inhibitors in melanoma, and ELM4-ALK inhibitors in lung cancer, along with the mechanisms of drug resistance and potential future strategies.