Correction: Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

[This corrects the article DOI: 10.1371/journal.pone.0277708.].

Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Obesity and sarcopenia have been reported to affect outcomes in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We analyzed prospective data from 52 patients with non-oncogene driven metastatic NSCLC treated with ICIs. Body tissue composition was calculated by measuring the fat and muscle densities at the level of 3rd lumbar vertebra in each patient computed tomography scan before ICI initiation using sliceOmatic tomovision. We converted the densities to indices [Intramuscular Fat Index (IMFI), Visceral Fat Index (VFI), Subcutaneous Fat Index (SFI), Lumbar Skeletal Muscle Index (LSMI)] by dividing them by height in meters squared. Patients were dichotomized based on their baseline IMFI, VFI and SFI according to their gender-specific median value. The cut-offs that were set for LMSI values were 55 cm2/m2 for males and 39 cm2/m2 for females. SFI distribution was significantly higher (p = 0.040) in responders compared to non-responders. None of the other variables affected response rates. Low LSMI HR: 2.90 (95% CI: 1.261-6.667, p = 0.012) and low SFI: 2.20 (95% CI: 1.114-4.333, p = 0.023) values predicted for inferior OS. VFI and IMFI values did not affect survival. Subcutaneous adipose and skeletal muscle tissue composition significantly affected immunotherapy outcomes in our cohort.

Chronic Central Serous Chorioretinopathy in a Patient with Pigment Dispersion Syndrome: A Possible Correlation.

Chronic central serous chorioretinopathy (CSCR) is a progressive chorioretinopathy with widespread atrophic RPE abnormalities and serous retinal detachments (SRDs) present for 6 months or longer. We report a case of CSCR in a 38-year-old patient with Pigment Dispersion Syndrome (PDS). In the presented case of CSCR, the chronic course of the disease may in part be associated with an underlying generalized degenerative dysfunction of the pigmented cells of the eye on grounds of PDS. We suggest that a chronic course of disease may be suspected in the setting of CSCR with concurrent RPE pathology, such as what is found in PDS.

Multiple spots of photodynamic therapy for the treatment of severe chronic central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy and safety of fluorescein angiography (FA)-guided photodynamic therapy (PDT) for the treatment of severe chronic central serous chorioretinopathy (CSC). METHODS: Patients presenting with chronic CSC with multiple areas of retinal pigment epithelium decompensation, with or without focal leaks, were treated with FA-guided full-fluence PDT. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), FA, indocyanine green angiography, and fundus autofluorescence were used to determine functional and anatomic outcomes. RESULTS: Twenty-one eyes (17 patients) were treated with PDT and followed for a median of 24 months (range, 12-73). In fourteen eyes (66.66%), two PDT spots were performed within the same session. In three eyes (14.28%), three PDT spots were performed, in two eyes (9.52%) four spots, and in two eyes (9.52%) five spots. In 17 eyes (80.95%), the leakage in FA and the subretinal fluid in OCT disappeared after only one session of PDT. In four eyes (19.05%), a second session - with only one spot - of PDT was required due to persistent or recurrent leakage and subfoveal SRF. Median BCVA improved significantly from 20/63 at baseline to 20/40 at 3 months (P = 0.0002) and 20/32 at 6 months (P < 0.0001), and remained improved until the last examination (20/25, P < 0.0001). Two patients complained of a transient central scotoma after the treatment. CONCLUSION: FA-guided full-fluence PDT with multiple PDT spots within the same session seems to be effective and safe for the treatment of chronic CSC cases with multiple areas of retinal pigment epithelium decompensation.

Second high-dose chemotherapy intensification followed by hematopoietic stem cell transplantation applying a novel high-dose topotecan-based regimen in an adult Wilms' tumor patient: case report.

High-dose chemotherapy and hematopoietic stem cell support remains a valuable treatment option for the rare patient population with relapsed Wilms' tumor. Here we report the case of a 22-year-old male patient treated with two cycles of high-dose chemotherapy at relapse after nephrectomy and adjuvant chemotherapy; the first cycle with melphalan--etoposide--carboplatin and the second with a novel preparative regimen incorporating high-dose topotecan (topotecan--cyclophosphamide--melphalan). A detailed discussion and literature review pertaining to that case is provided.

Double high-dose chemotherapy and stem cell transplantation in adult Wilms' tumor.

High-dose chemotherapy intensification and hematopoietic stem cell support remains a valuable treatment option for the rare patient with relapsed Wilms' tumor. We report a 22-year-old adult male with an initially diagnosed stage II Wilms' tumor, treated by nephrectomy followed by adjuvant chemotherapy. After 1 year, an intra-abdominal relapse was treated with salvage ifosfamide carboplatin etoposide chemotherapy followed by autologous hematopoietic stem cell mobilization. It was intended that he would receive two tandem cycles of high-dose chemotherapy; the first consisting of melphalan etoposide carboplatin; however, the patient did not return to receive the second cycle while in remission, but did return later with grossly relapsed disease. He was then treated with a novel preparative regimen incorporating high-dose topotecan (topotecan, melphalan and cyclophosphamide). This case confirms the feasibility of double high-dose chemotherapy with hematopoietic stem cell support in relapsed Wilms' tumor. A detailed discussion with an extensive review of the literature, regarding studies evaluating the role and indications of high-dose chemotherapy in Wilms' tumor is provided.

Malignant peripheral nerve sheath tumor in neurobifromatosis type-1: two case reports.

INTRODUCTION: Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas. They are considered to carry a poor prognosis with current therapeutic approaches. Successful treatment depends on a multimodal approach. CASE PRESENTATION: The authors report two cases with malignant peripheral nerve sheath tumors arising from pre-existing neurofibromas in the grounds of neurofibromatis-type I. Complete surgical removal of all lesions is considered before and after induction chemotherapy. Correlation of the response to chemotherapy in the context of the immuno-histopathological features of the tumors is also discussed with reference to the existing literature. CONCLUSION: A need for a multidisciplinary approach with chemotherapy, surgery and radiotherapy is anticipated in the management of malignant peripheral nerve sheath tumors as described in these two reported cases. It is felt that further research on the molecular aspects of malignant peripheral nerve sheath tumors and neurofibromatis-type I will optimize treatment strategies in the future.

Treatment strategies in CNS metastases.

BACKGROUND: CNS metastases constitute the most common brain malignancy in adults and, therefore, represent a challenging issue in cancer treatment. PURPOSE: To review the role and indication of the various treatment options in the context of important prognostic factors that may guide the selection of patients who could benefit from each treatment modality. METHODS: Therapeutic approaches in treating CNS metastases include surgery, radiotherapy and systemic chemotherapy, and are reviewed through a critical evaluation of published recent literature; however, in the majority of most common malignancies spreading to the CNS, treatment remains largely palliative and rarely curative, as is the case for other metastastic sites. CONCLUSIONS: It is anticipated that a multidisciplinary approach with rapid integration of new treatment strategies is required for the treatment of patients developing CNS metastases, ultimately aiming to prolong survival, preserve neurologic function and improve quality of life.

Docetaxel-ifosfamide combination in patients with HER2-non-overexpressing advanced breast cancer failing prior anthracyclines.

The feasibility of the docetaxel-ifosfamide combination, as well as the definition of maximum tolerated doses (MTD) in a previous phase I study, led us to continue evaluating the regimen in an extended phase II study in patients with HER2-non-overexpressing, anthracycline pre-treated advanced breast cancer. Patients with histologically confirmed metastatic breast cancer failing prior anthracycline-based chemotherapy were treated with docetaxel 100 mg/m2 over 1 h on day 1 followed by ifosfamide 5 g/m2 divided over days 1 and 2 (2.5 g/m2/day over 1 h), and recycled every 21 days with prophylactic granulocyte-colony stimulating factor (G-CSF) administration from day 3-until a neutrophil count >10,000/microl. Between March 1999 and June 2002, 71 patients with a median age of 55 years (range, 28-72) and performance status (World Health Organization; WHO) of 1 (range, 0-2) were treated; all were assessable for toxicity and 70 patients for response. Clinical response rates (RRs), on an intention-to-treat basis were: 41/71 [58%; 95% CI, 46.5-69.5%]; 7 complete remissions (CRs), 34 partial remissions (PRs), 15 stable disease (SD) and 15 progressive disease (PD). The median response duration was 7.5 months (2-28 months), median time-to-progression (TTP) 6 months (0.1-30 months), and median overall survival (OS) 12 months (0.1-36 months). Grade 3/4 toxicities included; neutropenia in 63% of patients-with 52% developing grade 4 neutropenia (>or=7 days) and in 11% of these febrile neutropenia (FN), while no grade 3/4 thrombocytopenia was observed. Other toxicities included; peripheral neuropathy grade 2 only in 7%, grade 1/2 reversible central nervous system (CNS) toxicity in 11%, no renal toxicity, grade 2 myalgias in 7%, grade 3 diarrhea in 4%, skin/nail toxicity in 11%, and grade 1/2 fluid retention in 28% of patients. The present report has demonstrated encouraging activity of the docetaxel-ifosfamide combination in anthracycline-pretreated, HER2-negative advanced breast cancer. Therefore, future randomized phase III studies versus single-agent docetaxel or currently established combinations of the latter with other agents in this setting with established clinical activity, such as capecitabine or gemcitabine, will be warranted.

A phase I-II study of bi-weekly gemcitabine and irinotecan as second-line chemotherapy in non-small cell lung cancer after prior taxane + platinum-based regimens.

PURPOSE: Treatment options in patients with recurrent non-small cell lung cancer (NSCLC) remain limited as a result of poor activity of most agents after failure of platinum-based therapy. In the present phase I-II study, we evaluated the feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in patients with relapsed NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, WHO-performance status (PS)

Diffuse calcification of metastases after intensive multiagent chemotherapy in widespread osteosarcoma leading to death in a 18-year-old male: report of a case and literature review.

Multifocal osteosarcoma represents a rare and aggressive type of osteosarcoma in which multiple bone lesions are detected simultaneously in the absence of pulmonary or any other visceral organ involvement. Despite a multidisciplinary approach, overall survival remains poor and disease progresses, leading to death within 1 yr of diagnosis. Here we report a case of an 18-yr-old patient with extensively metastatic osteosarcoma developing diffuse calcification in lung, pleural, diaphragm, pericardial, subcutaneous metastases, and mediastinal lymph nodes after intensive multiagent chemotherapy. We provide an extensive review of the literature together with presentation of different aspects regarding the debate on the multicentric versus metastatic hypotheses for multifocal osteosarcoma. An update on the current understanding of the molecular features of this disease is also included.

Cerebrospinal fluid tumor marker levels in predicting response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. MATERIAL/METHODS: Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. RESULTS: CSF tumor marker levels correlated with response to treatment and outcome in each patient; despite achieving negative CSF cytology after therapy, in two patients it heralded disease progression. CONCLUSIONS: Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.

Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer.

The aim of the present study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. CSF tumor marker levels correlated with response to treatment and outcome in each patient, and, despite achieving negative CSF cytology after therapy in two patients, it heralded disease progression. Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.