The Dilemma of Target Delineation with PET/CT in Radiotherapy Planning for Malignant Tumors

Currently there are many unanswered questions concerning contouring a target with PET/CT in radiotherapy planning.Who should contour the PET volume-the radiation oncologist or the nuclear medicine physician?Which factors will contribute to the dual-observer variability between them?What should be taken as the optimal SUV threshold to demarcate a malignant tumor from the normal tissue?When the PET volume does not coincide with the local area CT findings,which portion should be contoured as the target?If a reginal lymph node draining area or a remote region is shown to be PET positive but CT negative,or PET negative but CT positive,how is the target identified and selected?Further studies concerning the relationship between PET/CT and the cancerous tissue are needed.The long-term clinical results showing an increased therapeutic ratio wil finaly verify the applicability of guidelines to contour the target with PET/CT in radiotherapy planning.     

Ultrasound Operators’ Confidence Influences Diagnosis of Ovarian Tumors - a Study in China

Aim: To assess the effect of ultrasound operators’ confidence in diagnosis of ovarian cancer, and the factorsinfluencing diagnostic accuracy. Methods: Ultrasound images of selected ovarian cancers and controls wereevaluated by 8 sinologists who were instructed to diagnose and classify lesions into benign, borderline ormalignant, and we use structured questionnaire to investigate the level of confidence. We analyzed the accuracyof diagnosis, including sensitivity, specificity, positive and negative likelihood ratios and accuracy dependingon the different levels of confidence. In addition, factors influencing diagnostic accuracy was assessed bylogistic regression analysis. Results: A total of 426 cases were examined. The confidence score was significantlyincreased with the level of accuracy (test for trend, p<0.05). Borderline tumors were most difficult to diagnose,and had lower accuracy, sensitivity and specificity compared with benign and primary invasive tumors. Workingexperience was positively closely associated with diagnosis accuracy. Logistic regression analysis revealed workingexperience and confidence score to be positively related to the diagnostic accuracy(OR, 95%CI, 1.68, 1.15-3.97for working experience; OR, 95%CI, 3.75, 1.67-6.98 for confidence score). Conclusion: Our study showed thatlevel of confidence is positively associated with diagnostic performance, and the accuracy is greatly influencedby working experience and confidence score.     

Is There Still a Role for Axillary Dissection in Breast Cancer Surgery?

The operative management of breast cancer has followed a natural progression toward less invasive techniques over the past century as chemotherapy, hormonal therapy, and radiation therapy have become more effective and used more frequently. Sentinel lymph node (SLN) biopsy in clinically node-negative patients has replaced axillary lymph node dissection (ALND), resulting in improved staging and decreased morbidity. ALND has remained important for patients with clinically involved lymph nodes or positive SLN; however, new evidence from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial has identified a subset of patients with breast cancer who do not benefit from axillary lymphadenectomy following a positive SLN biopsy. These results are practice changing and need to be analyzed within the context of patient selection and multidisciplinary treatment. Herein, we review the emerging data regarding the benefits and indications for axillary lymphadenectomy in the modern era of multidisciplinary breast cancer management.     

What Is the Place of PARP Inhibitors in Ovarian Cancer Treatment?

Poly-ADP-ribose polymerase (PARP) inhibitors have been one of the most exciting developments in the treatment of ovarian cancer in recent years. Demonstration of anti-cancer activity has led to the European Medicines Agency (EMA) approval of the PARP inhibitor (PARPi) olaparib as maintenance therapy in women with BRCA-mutated (BRCAm) ovarian cancer with platinum-sensitive recurrence following response to platinum therapy and the US Food and Drug Administration (US FDA) approval of olaparib in relapsed germline BRCA-mutated (gBRCAm) ovarian cancer in women who have received at least three prior chemotherapy treatments, both occurring in 2014. Additional trials are underway or awaiting final analysis with olaparib, other PARPis, and PARPi combinations to further elucidate the activity of these drugs in various clinical settings. This review will focus on the current clinical experience and ongoing trials with PARPis in ovarian cancer.     

What Is the Benefit of Bevacizumab Combined with Chemotherapy in Patients with Recurrent Ovarian,Fallopian Tube or Primary Peritoneal Malignancies?

Abstract

The aim of this retrospective analysis was to investigate the efficacy and adverse effects of the monoclonal anti vascular endothelial growth factor antibody bevacizumab (Avastin^®) combined with chemotherapeutic agents in non-protocol patients with recurrent ovarian, fallopian tube, or primary peritoneal malignancies. Using our data-bases, we identified patients treated with bevacizumab combination therapy since June2005. Responses were evaluated with Response evaluation Criteria in Solid tumorsand serum CA125 Rustin criteria. Toxicity was assessed according to the Commontoxicity Criteria (CTC) v.3.0. Data from 64 patients were included. The median patient age was 58 years, and they had undergone a median of 4.5 (range, 1-10) prior cyto-toxic chemotherapy regimens. The median length of follow-up was 8 months (range, 2-29). The most commonly used combinations were bevacizumab plus taxanes (26.6%) and plus cyclophosphamide (26.6%). A median of 4 cycles of therapy with a medianbevacizumab dose of 3,600 mg (range, 500-18,240) were administered. An overallresponse rate of 21.3% was observed in 13 patients with partial response, and an-other 42.6% of patients had stable disease. Among the patients with elevated pre-treatment serum CA125 concentration, an overall response rate of 46.3% (25/54) was observed according to modification of the Rustin criteria. Fifteen (23.4%) patients had grades 3 or 4 adverse events. Gastrointestinal perforations occurred in 2 (3.1%) patients. Seventeen (26.6%) patients had improved performance status scores. Beva-cizumab combined with chemotherapy showed promising clinical benefits, with significant response of serum CA125 concentration and moderate adverse effects.     

What Is the Role of Radiotherapy in Malignant Pleural Mesothelioma?

Objective.

A review of the evidence supporting the use of radiotherapy in patients with mesothelioma was performed.

Methods.

Relevant publications were searched for on Medline.

Results.

In a Medline search on radiotherapy and mesothelioma, 611 hits were obtained. A limited number of prospective phase II trials of radiotherapy as part of trimodality protocols for early disease and in the palliation of pain were found, along with three small randomized controlled trials of port-site prophylaxis.

Conclusion.

No randomized data exist to support the use of radiotherapy after radical surgery, although there are a large number of publications describing its use as an integral part of therapy, including seven phase II studies. One ongoing trial is randomizing patients to radiotherapy or not after extrapleural pneumonectomy. None of these studies provided any assessment of radiotherapy independent of the other modalities investigated, nor did any formally assess intensity-modulated radiotherapy. There have been several reports of excessive toxicity with this technique, and its use should be limited to phase I studies until the basis of this toxicity is better understood. Three trials have looked at port-site prophylaxis, one supporting its use and two showing no evidence of benefit. Two studies addressed pain control prospectively, one showing definite but short-lived benefits.

Implications.

Radiotherapy is widely used in treating mesothelioma with little supporting evidence. More randomized trials are required to justify this use in all three common settings for its use.     

Is a Single Respiratory Correlated 4D-CT Study Sufficient for Evaluation of Breathing Motion?

PURPOSE: Respiratory correlated computed tomography has been shown to be effective for evaluation of breathing-induced motion of pulmonary tumors. This study investigated whether a single four-dimensional CT study (4D-CT) is representative and sufficient for treatment planning in stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Four repeated helical 4D-CT studies were acquired every 10 min for 10 patients with 14 pulmonary metastases. Patients remained immobilized in a stereotactic body frame (SBF) for 30 min; abdominal compression was applied to seven patients. Using amplitude based sorting, eight phases equally distributed over the breathing cycle were reconstructed for each 4D-CT study. Tumor position was defined in a total of 406 CT series and variability of breathing motion and mean tumor position were evaluated. RESULTS: Peak-to-peak tumor motion was 9.9 mm +/- 6.8 mm (mean +/- standard deviation) and 9.0 mm +/- 7.4 mm at time point 0 min (t(0)) and t(30), respectively. In one patient with poor pulmonary function, continuous increase of breathing motion from 17.4 mm at t(0) to 28.3 mm at t(30) was seen. In five and two lesions, respectively, a drift of the mean tumor position greater than 3 mm and 5 mm was observed. A borderline significance was calculated for larger tumor position variability in midventilation phases compared with peak-ventilation phases of the breathing cycle (p = 0.08). CONCLUSION: Treatment planning based on a single 4D-CT study is reliable for the majority of patients. Increased intrafractional uncertainties were seen for patients with poor pulmonary function and with tumors located in the lower lobe.     

Is Renal Thrombotic Angiopathy an Emerging Problem in the Treatment of Ovarian Cancer Recurrences?

Background and Objective.

Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions.

Patients and Methods.

Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997–2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002–2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m² for >3 months and were staged according to the National Kidney Foundation guidelines.

Results.

Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy.

Conclusions.

CKD is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.     

What Is the Role of Chemotherapy in Patients With Chronic Lymphocytic Leukemia?

The current standard treatment for patients with chronic lymphocytic leukemia who require therapy is chemoimmunotherapy. However, the availability of an increasing number of targeted agents and combination warrants a reassessment of that approach. The high rate of durable responses with ibrutinib in relapsed refractory patients has established its role in this setting; however, because of its impressive efficacy as initial treatment, it should be considered as part of the algorithm in appropriate patients. There is virtually no role for chemotherapy in the relapsed or refractory setting, but, instead, consideration of active agents including idelalisib plus rituximab, or, particularly venetoclax. For patients with 17p-deletion, ibrutinib is the treatment of choice, with venetoclax in the setting of intolerance or relapse. Challenges include developing strategies to limit the duration of these expensive therapies, and to develop combinations with the potential to cure patients with chronic lymphocytic leukemia.     

The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial,Germ Cell,and Mesenchymal Tumors?

This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1^high phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.     

Comprehensive Gene Mutation Profiling of Breast Tumors: Is It Ready for Prime Time Use?

Recent advances in molecular biology have led to unprecedented innovations in diagnosis and treatment of breast cancer. The advent of genomics has revolutionized our understanding of breast cancer. It is no longer considered a single disease but several different biologically and molecularly distinct entities. This research has led to commercially available polymerase chain reaction (PCR)-, microarray-, and next generation sequencing (NGS)-based tests which have changed the way oncologists estimate recurrence risk in early stage breast cancer patients. The genomics era has altered the clinicopathologic paradigm of selecting patients for adjuvant cytotoxic chemotherapy. Numerous well designed prospective studies are underway that may establish these molecular assays as basic elements of standard clinical practice in breast cancer diagnostics and therapeutics. In this article, we review the robustnesses and constraints of currently available breast cancer-specific molecular tests and their clinical ramifications.     

Oncoplastic Surgery in Surgical Treatment of Breast Cancer: Is the Timing of Adjuvant Treatment Affected?

IntroductionWith the results of studies on the timing of adjuvant treatment, it currently appears that adjuvant treatment should be initiated as soon as possible. Breast conserving surgery and oncoplastic surgery is being used with increasing frequency. Therefore, studies about whether or not these applications delay the adjuvant treatment are needed. The aim of this study was to determine the time period needed for adjuvant chemotherapy and radiotherapy of the patients with breast cancer and to reveal associated factors related to the patient, tumor, and surgical technique.Patients and MethodsTwo hundred eighty patients with breast cancer who had surgery and were given adjuvant treatments in our clinic were included in the study. Age, body mass index, concomitant diseases, smoking habits, menopausal status, neoadjuvant treatments, tumor characteristics, surgical technique, and surgical complications were recorded. The time period between surgery and initiation of chemotherapy and radiotherapy, the number of chemotherapy cycles, and the duration of chemotherapy and radiotherapy were calculated.ResultsThe numbers of patients who had modified radical mastectomy, breast conserving surgery, and oncoplastic surgery were 155 (55%), 47 (16.8%), and 78 (27.9%), respectively. The mean (SD) time period needed for chemotherapy administration was 19.5 ± 4.2 days (range, 13-41 days) and 3.9 ± 0.9 months for radiotherapy. Early wound complication of breast surgery was the only factor that delayed the adjuvant chemotherapy (P = .001).DiscussionIt has been well known that the time period between surgical treatment of breast cancer and adjuvant treatment affects survival. In our study, it has been shown that the surgical techniques used in breast and axillary surgery do not delay the initiation of adjuvant treatments. The adjuvant treatments of the patients who had oncoplastic surgery and breast conserving surgery were not delayed. The cooperation between the disciplines for the initiation of adjuvant treatments is important.