Neoadjuvant Treatment of Locally Advanced Soft Tissue Sarcoma of the Limbs: Which Treatment to Choose?

Soft tissue sarcomas (STSs) form a heterogeneous group of malignant neoplasms arising in the mesenchymal connective tissues. They can develop at any anatomic site but 60% occur in the extremities. Initially, treatment of STS relied solely on excision. In the 1970s, Enneking et al. developed the concept of compartmental resection to reduce the local failure rate. Later, Rosenberg et al. demonstrated, in a randomized study, that there was no difference in local tumor control and disease-free survival (DFS) in patients treated with amputation versus limb-saving surgery followed by 50-70 Gy external-beam radiotherapy (EBRT). A considerable proportion of patients present with locally advanced tumors as a primary or recurrent disease and cannot be resected with adequate clearance margins. These patients are threatened with amputation for complete tumor removal. Improvements in surgical techniques, such as microvascular muscle flaps, allow for the avoidance of limb loss in the majority of cases. However, the use of frozen sections to determine intraoperatively whether clear margins have been achieved is limited by the multiplanarity of resection specimens. Thus, local failure rates are 15%-25%, and preoperative measures to sterilize the invasive margin of sarcomas have been explored. High-dose preoperative EBRT for high-grade STS was developed, and its combination with intra-arterial or i.v. chemotherapy was reported to be effective. Recently, systemic chemotherapy combined with deep wave hyperthermia was shown to result in a longer DFS time in a large, randomized, phase III study. Treatment concepts differ significantly among centers and are influenced more by availability of technical equipment than by data. It is the aim of this review to elucidate the rationale of different regimens and analyze their potentials as well as weaknesses.     

What Goals Do Patients and Oncologists Have When Starting Medical Treatment for Metastatic Lung Cancer?

BackgroundMetastatic lung cancer is an incurable disease that can be treated with systemic therapy. These treatments might prolong survival and reduce symptoms, but they may also cause serious adverse effects. We studied the treatment goals of patients with metastasized lung cancer and their oncologists before starting systemic therapy, concordance between patients’ and oncologists’ goals, and feasibility of these goals.Patients and MethodsThis research was conducted between November 2016 and April 2018 in 1 academic and 5 nonacademic hospitals across the Netherlands. A total of 266 patients with metastatic lung cancer and their prescribing oncologists (n = 23) filled out a questionnaire about their treatment goals and the estimated feasibility of these goals before treatment was started. Additional interviews were conducted with patients and oncologists.ResultsPatients and oncologists reported quality of life (respectively, 45% and 72%), life prolongation (45% and 55%), decrease in tumor size (39% and 66%), and cure (19% and 2%) as treatment goals. The interviews showed that the latter appeared to be often as motivation to stay alive. Concordances between patients’ and oncologists’ treatment goals were low (ranging from 24% to 33%). Patients had slightly higher feasibility scores than oncologists (6.8 vs. 5.8 on a 10-point scale). Educational level, age, religious views, and performance status of patients were associated with treatment goals.ConclusionPatients and oncologists set various goals for the treatment they receive/prescribe. Low concordance might exist because different goals are set or because the patient misunderstands something. Clear communication about treatment goals should be integrated into clinical care.     

Rituximab Maintenance Versus Radioimmunotherapy Consolidation in Follicular Lymphoma: Which, When, and for Whom?

Follicular lymphoma (FL), the most common indolent lymphoma, typically presents in advanced-stage disease. Currently available therapy does not generally result in a curative outcome, but survival in FL has improved since the introduction of anti-CD20 monoclonal antibody immunotherapy. The goals of treatment include prolongation of survival and effective palliation of symptoms while limiting the duration of therapy to minimize adverse effects and reduce costs. Multiple rounds of treatment over many years characterize the clinical course for most patients with FL. Rituximab in combination with chemotherapy has been shown to improve overall survival in patients with FL compared with chemotherapy alone. Rituximab maintenance further improves disease control in patients with FL after a successful induction therapy in both first-line treatment and relapse. Consolidation with radioimmunotherapy is an innovative treatment approach to increase rates of complete remission and duration of remission. Here we summarize the data from actual trials and the resulting treatment indications.     

Chemotherapy for Stage IV Non-Small Cell Lung Cancer: Protocol Versus Nonprotocol? Is Noninvestigational Treatment Worthwhile? Patient Selection? Which Regimen? What's Next?

The results of selected chemotherapy trials and philosophical considerations regarding the role of chemotherapy in Non-Small Cell Lung Cancer are discussed in this review. The issue of treating patients within a clinical or with a "standard regimen" is addressed. In addition, the survival results of randomized trials in which chemotherapy was compared with supportive care and the related quality of life and economic concerns are reviewed. Physicians' attitudes regarding treating advanced non-small cell lung cancer patients as well as the questions of patient selection and the choice of regimen including the consideration of single versus combination regimens are discussed. The results of single agent phase II trials that identified new agents with response rates >/=15%-paclitaxel, docetaxel, vinorelbine, gemcitabine, CPT11-are described, and their implications for the design of new clinical trials are discussed.     

When is precancerous actually postcancerous?

Demonstration that certain rare cancer-related mutations can (i) be shared by adjoining benign and cancerous tumor regions or (ii) be present solely in a cancerous but not in an adjoining benign tumor region are data often cited in strong support of the conventional idea that benign tumor regions consist of precancerous cells. However, considering the well-documented evidence that many malignant cell types are still capable of regression through differentiation, one can envisage an alternative (or coincident) scenario whereby (i) mutations are shared by adjoining benign and cancerous tumor regions because a cancer cell with a non-differentiation-impairing mutation differentiates into a benign (postcancerous) cell or (ii) mutations are present solely in a cancerous tumor region because a cancer cell acquires a differentiation-impairing mutation that prevents its regression into a benign cell. Only with higher-resolution lineage analyses of a type not yet performed but experimentally feasible can these scenarios be distinguished. Accordingly, it is quite possible that common cancers regularly differentiate, such that a benign tumor region may actually harbor not only precancerous but also postcancerous cells. Demonstration of this phenomenon and elucidation of its mechanism could lead to novel therapeutics designed to effect reversion of the more common cancers that, when in advanced stages, are notoriously inadequately treated by current cytotoxic regimens.     

Which women decide to take tamoxifen?

Purpose

To identify factors which predict, among estrogen receptor (ER)-positive breast cancer patients, who chooses to take adjuvant tamoxifen.

Methods

We studied 1347 women with ER-positive breast cancer who were treated at Women’s College Hospital between 1987 and 2000. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, ER status, treatments received and dates of local recurrence and of death. We compared women who did and who did not take tamoxifen for a range of factors. We used the Kaplan–Meier method to estimate 15-year local recurrence-free and breast cancer-specific survival rates for women who did and who did not take tamoxifen.

Results

Overall, 50.4% of women who had a mastectomy took tamoxifen and 61.0% of women who had a lumpectomy took tamoxifen (p = 0.002). Tamoxifen use did not correlate with any of the factors that were predictive of a high risk of death from breast cancer, such as young age, large tumour size and positive lymph node status. Young women (<40 years) experienced much higher mortality (41.1%) than older (>60 years) women (14.1%, p < 0.01), but were much less likely to have taken tamoxifen (35.0 vs. 74.6%, p < 0.01).

Conclusions

Approximately one-half of women with ER-positive breast cancer who are candidates for tamoxifen did not take tamoxifen. Women with lumpectomy were more likely to take tamoxifen than women with mastectomy. Paradoxically, women at high risk of death from breast cancer (less than 40 at diagnosis and/or lymph node positive) and who are expected to receive the greatest benefit from tamoxifen in terms of mortality reduction were less likely to take it than were low-risk women (older women, lymph node negative). These findings suggest that women consider the reduction in risk from local recurrence to be more important than the reduction in risk of death from breast cancer when they consider taking tamoxifen.

     

When is transanal endoscopic surgery appropriate?

Rectal cancer is a complex medical diagnosis which requires critical decision-making on the part of physician and patient. Organ preservation with local excision for early stage rectal cancer, if done under the correct circumstances, allows for oncologically sound surgery with good patient outcomes. However, locally advanced disease as well as tumor location and size can change potential long-term outcomes. This article will investigate the technical and clinical aspects of transanal surgery and the decision-making algorithms for clinicians and patients.     

Which Endometrial Pathologies Need Intraoperative Frozen Sections?

Background: Endometrial cancers are the most common gynecologic cancers. Endometrial sampling is apreferred procedure for diagnosis of the endometrial pathology. It is performed routinely in many clinics priorto surgery in order to exclude an endometrial malignancy. We aimed to investigate the accuracy of endometrialsampling in the diagnosis of endometrial pathologies and which findings need intra-operative frozen sections.Materials and Methods: Three hundred nine women applying to a university hospital and undergoing endometrialsampling and hysterectomy between 2010 and 2012 were included to this retrospective study. Data were retrievedfrom patient files and pathology archives. Results: There was 17 patients with malignancy but endometrialsampling could detect this in only 10 of them. The endometrial sampling sensitivity and specificity of detectingcancer were 58.8% and 100%, with negative and positive predictive values of 97.6%, and 100%, respectively. In7 patients, the endometrial sampling failed to detect malignancy; 4 of these patients had a preoperative diagnosisof complex atypical endometrial hyperplasia and 2 patients had a post-menopausal endometrial polyps and 1with simple endometrial hyperplasia. Conclusions: There is an increased risk of malignancy in post-menopausalwomen especially with endometrial polyps and complex atypia hyperplasia. Endometrial sampling is a goodchoice for the diagnosis of endometrial pathologies. However, the diagnosis should be confirmed by frozen sectionin patients with post-menopausal endometrial polyps and complex atypia hyperplasia.     

Rectal cancer adjuvant therapy controversies: When? What? Why?

Although the need for adjuvant therapy in high-risk rectal cancer is widely accepted, controversies continue regarding timing, mode, and agents employed. The current recommended practice and its scientific basis are reviewed. Studies of induction therapy are discussed. Evidence of efficacy of new anticancer agents and modes of drug delivery are presented.     

Which individuals undergoing BRACAnalysis need BART testing?

Deleterious mutations in BRCA1 and BRCA2 include those identified by sequencing technology as well as large genomic rearrangements (LGR). The main testing laboratory in the United States, Myriad Genetics Laboratory (MGL), has defined criteria for inclusion of LGR testing (i.e., BRACAnalysis Rearrangement Test, or BART?) when BRCA1 and BRCA2 testing is ordered. We were interested in determining how many of our patients with LGR mutations in BRCA1 and BRCA2 fulfilled these MGL criteria. A retrospective chart review was performed on all individuals who underwent genetic testing at our institution since August 2006. Individuals who underwent LGR testing were classified as either having or not having a LGR in BRCA1 or BRCA2. Each individual's history was classified as meeting MGL defined LGR criteria, meeting criteria using third-degree relatives, or not meeting criteria. A total of 257 BART tests were ordered at our institution from August 2006 to August 2009. Five individuals (1.9%) had an LGR mutation. Two LGR were identified in patients who met MGL defined LGR criteria. One LGR was identified in a patient that met MGL defined LGR criteria only when using third-degree relatives. Two LGR were identified in individuals who did not meet MGL defined criteria. LGR are present in individuals who do not have a high pretest probability of carrying a mutation in BRCA1 or BRCA2. These data suggest that when BRCA1 and BRCA2 genetic testing is performed, testing should always include LGR testing so that the results are the most comprehensive and reliable.