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Over the past 5 years, several studies have investigated the molecular profiling of penile carcinomas, examining both genomic and epigenetic alterations. These studies have revealed distinct molecular pathways associated with HPV status.

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In this review, we examine the currently approved options available for these disease processes, including the newer agents and selected combinatorial approaches under investigation, and we attempt to identify the role of high-dose IL-2 in the context of current clinical practice.

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The development of metastatic disease in patients with paraganglioma is an unusual and challenging event. This case report and review describes the specific features of this disease and the multiple therapeutic options.

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More than 60 years ago, Karnofsky and colleagues reported promising results with the introduction of nitrogen mustard, the prototype of alkylating agents, for the treatment of lung cancer.[1] Subsequent milestones in the development of lung cancer chemotherapy included the use of platinum agents in the 1970s and 1980s, while the 1990s brought several active agents that could be combined with platinum, namely the taxanes, gemcitabine (Gemzar), and vinorelbine.

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The review by Drs. Ruta Rao and Melody Cobleigh in this issue of ONCOLOGY summarizes the state-of-the-art adjuvant hormonal therapy for breast cancer concisely and appropriately.

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The prospect of even more compressed radiotherapy options for women requiring adjuvant breast radiotherapy is exciting. However, we urge readers to be cautious in their interpretation of the current intraoperative literature as they implement their programs.

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This testicular cancer management guide covers the diagnosis, staging, and treatment of germ-cell tumors and seminoma.

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Among patients with lung cancer, approximately 15% have smallcelllung cancer (SCLC). The clinical characteristics of SCLC tend tobe more aggressive, but also more sensitive to chemotherapy and radiationtherapy than those of non-SCLC. Irinotecan (Camptosar) is aderivative of camptothecin, an inhibitor of the nuclear enzymetopoisomerase I. Irinotecan has been shown to exhibit excellent antitumoractivity against SCLC in monotherapy regimens and in combinationwith cisplatin. A phase III trial comparing irinotecan and cisplatin(IP) with etoposide and cisplatin (EP) in patients with previously untreatedextensive-stage SCLC (ED-SCLC) was conducted. Patients inthe IP arm responded significantly better than patients in the EP arm.In the IP arm, the response rate was 84%, and median overall survivalwas 12.8 months. A phase II trial of irinotecan, cisplatin, and etoposide(IPE) administered weekly (arm A) or every 4 weeks (arm B) for EDSCLC(JCOG 9902-DI) was also performed. In arm B, the responserate was 77% and the median overall survival was 12.9 months. A randomizedtrial comparing IP with IPE administered every 3 weeks inpatients with previously untreated ED-SCLC is presently being performedin Japan.

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In this video, Dr. Atsushi Ohtsu discusses the use of TAS-102, an oral combination of trifluridine and tipiracil hydrochloride, in refractory colorectal cancer.

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Cancer patients experience pain in multiple sites and from several pathophysiologies of the symptom complex. The fluctuating nature of cancer pain intensity is a relevant clinical feature and depends on disease patterns and pain mechanisms. Breakthrough pain is defined as episodes of pain that "break through" the control of an otherwise effective analgesic therapy.

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The patient is an otherwise healthy 45-year-old female who presented to her primary care physician with 6 weeks of increasing left upper quadrant abdominal pain with radiation to the back. She underwent an abdominal ultrasound, which revealed a large cystic abdominal mass.

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It is clear that in a subset of patients with GI malignancies, particularly the low-grade appendiceal neoplasms, CS + HIPEC can result in improved outcomes and in some cases, long-term remission and occasionally cure.

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The review by Kahn andJohnstone published in this issueof ONCOLOGY is comprehensiveand interesting. A fewpoints deserve emphasis, the first ofwhich is the issue of how we shouldmeasure and report xerostomia. Accurateand reliable measurements ofxerostomia are necessary in order toproperly assess its severity, timecourse, dose-response relationships,and the efficacy of measures to protectthe glands or to stimulate salivaryproduction following irradiation. Xerostomiaencompasses the objectivereduction in salivary output andchanges in its composition, as well asthe subjective symptoms reported bythe patient. Currently available measurementsof xerostomia include(1) functional imaging of gland activity,(2) measurements of the salivaryoutput, (3) observer-assessed toxicitygrading, and (4) instruments assessingpatient-reported evaluation of thevarious xerostomia-related symptoms.

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There is clear proof of principle for adjuvant therapy in patients at high risk for tumor recurrence, such as those with resected metastatic colorectal cancer. For that reason, this strategy has been largely adopted, especially using 5-FU– and oxaliplatin-based regimens, thereby mirroring the approach in resected stage III colon cancer.

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Whether patients with clinical stage I nonseminomatous testicular germ-cell cancer (NSGCT) should be treated with orchiectomy and retroperitoneal lymph node dissection (RPLND) or orchiectomy and surveillance remains

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Pemetrexed (Alimta) is a novel folate antimetabolite that primarilyinhibits the enzymes thymidylate synthase (TS), dihydrofolate reductase(DHFR), and glycinamide ribonucleotide formyl transferase(GARFT), all of which are involved in pyrimidine and purine synthesis.In a phase II trial of patients with T3/4, N0–2 breast cancer, expressionof thymidylate synthase (TS), dihydrofolate reductase (DHFR),glycinamide ribonucleotide formyltransferase (GARFT), p53, andc-erb-B2 (at the mRNA or protein level) was examined in tumor biopsyspecimens before and 24 hours after the first dose of pemetrexed andafter three cycles of single-agent treatment to establish correlations ofbiomarker levels and changes with clinical outcome and toxicity. Althoughfinal data are not available, initial indications are that clinicalresponse may correlate with decreased or low TS expression. The resultsobtained from clinical data are supported by laboratory results inthree cell lines (MDA-231, MCF-7, and ZR-75). These results suggestthat in vitro transcript profiling to identify which genes are importantpredictors of successful cytotoxic chemotherapy, followed by a focusedclinical trial to confirm the in vitro results, may be the best approachfor translational research.

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Closing out their review of the HER2+ metastatic breast cancer treatment landscape, expert oncologists look forward to future evolutions in the paradigm.

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Since the topic of risk-stratified management of patients with myelodysplastic syndromes (MDS) was last reviewed in ONCOLOGY in 2007,[1] a few additional clinically relevant studies have emerged that can help inform decision-making in the consultation room.

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Along with various imaging modalities, serologic tumor markers such as CA 15-3 and CA 27.29 have been used for decades to monitor treatment response in patients with metastatic breast cancer (MBC). Despite the frequent use of these markers, they lack high sensitivity and specificity for breast cancer progression. The prognostic significance of these markers remains indeterminate because of the conflicting outcome of many clinical trials. The circulating tumor cell (CTC) test has recently been studied in clinical trials in patients with MBC. Some of the studies showed that high levels of CTCs are correlated with poor survival in MBC. An intergroup trial is underway to determine the implication of changing treatment based on the CTC level. This article will discuss the current data on these markers, with special emphasis on the CTC test. The potential clinical utility of these markers will also be discussed.

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Dr. Krasna provides a well-illustrated review of the applications of thoracoscopy in lung and esophageal tumors. These include: staging of tumors; diagnosis of indeterminate pulmonary nodules; definitive resections of various tumors, especially in cases of poor reserve; and diagnosis and treatment of malignant pleural disease [1]. However, there remains considerable disagreement among thoracic surgical oncologists over the proper applications of these techniques.

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Intracranial germinomas are uncommon tumors. In the past, patients have traditionally been diagnosed with a trial of focal radiotherapy without biopsy. If the tumor was radiosensitive, it was presumed to be a germinoma.

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Ibritumomab tiuxetan (Zevalin) consists of an anti-CD20 murine IgG1 kappa monoclonal antibody covalently bound to tiuxetan (MX-DTPA), which stably chelates yttrium-90 for therapy. Ibritumomab tiuxetan therapy involves pretreatment with

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Rituximab (Rituxan), when combined with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy (R-CHOP) in the treatment of patients with CD20-positive diffuse large B-cell lymphoma (DLCL), significantly prolongs event-free and overall survival (GELA [Groupe d’Etude des Lymphomes de l’Adulte] LNH 98-5 study). Our objective was to estimate the cost-effectiveness of R-CHOP based on the evidence currently available.

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Rituximab (Rituxan) has shown high activity in relapsed follicular lymphomas when given alone, and phase II studies indicate that its addition to chemotherapy may further improve response rates substantially. Because prospective randomized studies have not been available so far, the German Low Grade Study Group (GLSG) started a multicenter national trial in patients with relapsed or refractory follicular cell lymphoma (FCL) or mantle cell lymphoma (MCL). As patients were treated for first-line therapy with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone), the FCM (fludarabine [Fludara], cyclophosphamide, mitoxantrone [Novantrone]) combination was chosen for salvage chemotherapy.

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Mendenhall and colleagues provide a useful review of the management of squamous cell carcinoma of the anal margin. Although I generally agree with their conclusions and recommendations for treatment, their paper highlights the continuing difficulties in developing a universally agreed-upon descriptive terminology for the anal region.

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The world’s population is aging. Older age is associated with an increase in the incidence of cancer, especially cancer of the breast, lung, prostate, and colon. The management of older patients with cancer is biased by the

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This study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastaticbreast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) incomparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those withmetastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapyfor metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, openlabel,phase II study in Germany. A control group of 23 patients received EC 90/600 mg/m2 3-weekly for sixcycles (EC90 alone). A total of 26 HER2-positive patients were treated with trastuzumab, or H (2 mg/kg weeklyafter an initial loading dose of 4 mg/kg), and EC 60/600 mg/m2 3-weekly for six cycles (EC60+H); another 25HER2-positive patients received H and EC 90/600 mg/m2 3-weekly for six cycles. Asymptomatic reductions inleft ventricular ejection fraction (LVEF) of more than 10% points were detected in 12 patients (48%) treatedwith EC60 + H and in 14 patients (56%) treated with EC90 + H vs 6 patients (26%) in the EC90 alone cohort.LVEF decreases to < 50% occurred in one patient in the EC60+H cohort and in two patients in the EC90+Hcohort during the H monotherapy. No cardiac event occurred in the cohort with EC90 alone. The overallresponse rates for EC60+H and EC90+H were >60%, vs 26% for EC90 alone. The interim results of this studysuggest the cardiac safety of the combination of H with EC may be greater than that of H with AC (doxorubicin[Adriamycin]/cyclophosphamide); however, studies in larger numbers of patients are warranted. The combinationregimen revealed promising efficacy.

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We previously reported the efficacy of concurrent cisplatin (Platinol)/etoposide (PE) and radiotherapy in stage IIIB non–small-cell lung cancer in which biopsy confirmation of T4 (noneffusion) or N3 status was required (S9019). In view of the activity of docetaxel (Taxotere) as second-line therapy and potential molecular mechanisms of action favoring taxane sequencing, we designed the present study to maintain a core of concurrent PE/radiotherapy, but to substitute docetaxel consolidation for the two additional cycles of PE.