“How Long Have I Got?” in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question

BackgroundMost lung cancer patients worldwide [stage IV nonsmall cell lung cancer (NSCLC)] have a poor survival: 25%–30% die <3 months. Yet, of those surviving >3 months, 10%–15% (70,000–105,000 new patients worldwide per year) survive (very) long. Surprisingly, little scientific attention has been paid to the question, which factors cause the good prognosis in these NSCLC stage IV long survivors. Therefore, “How long do I still have?” currently cannot be accurately answered. We evaluated in a large group of 737 stage IV NSCLC patients surviving 3.2–120.0 months, the accuracies of short- and long-term survival predictive values of baseline factors, radiotherapy (RT), platinum-based chemotherapy (PBT), and tyrosine kinase inhibitor targeted therapy (TKI-TT).MethodsThis is a noninterventional study of 998 consecutive first-onset stage IV NSCLC patients. A total of 737 (74%) survived 3.2–120.0 months, 47 refused RT, PBT, and TKI-TT. Single and multivariate survival analysis and receiver operating curve (ROC) analysis were used with dead of disease (DOD) or alive with disease (AWD) as endpoints.ResultsThe median survival (16.1 months) of 47 patients who refused PBT, RT, and TKI-TT was significantly worse than those with RT, PBT, and/or TKI-TT (23.3 months, HR = 1.60, 95% CI = 1.06–2.42, p = 0.04). Of these latter 690 patients, 42% were females, 58% males, median age 63 years (range 27–85), 1-, 2-, 5-, and 10-year survival rates were 74%, 49%, 16%, and 5%. In total, 16% were alive with disease (AWD) at the last follow-up. Pathology subtype (adenocarcinoma vs. all others), performance score, TNM substage, the number of PBT cycles and TKI-TT had independent predictive value. However, with the multivariate combination of these features, identification results of short-term nonsurvivors and long-term survivors were poor.ConclusionsIn stage IV NSCLC patients with >3 months survival, baseline features, and systemic therapeutic modalities have strong survival predictive value but do not accurately identify short- and long-term survivors. The predictive value of other features and interventions discussed should be investigated in the worldwide very large group of stage IV NSCLC patients with >3 months survival.

Exploring the association with disease recurrence of miRNAs predictive of colorectal cancer

Introduction Disease recurrence after surgery is a crucial predictor of poor prognosis in colorectal cancer, where disseminated disease at the time of intervention can also be observed in localized early-stage cases. We evaluated the ability to predict disease recurrence of miRNAs from two signatures that we have found linked to the presence of colorectal cancer (CL signature) or adenoma (HgA signature) in higher-risk subjects. Methods miRNAs from the signatures were studied longitudinally by quantitative real-time polymerase chain reaction in plasma from 24 patients with resectable colorectal cancer collected at the time of surgery and during scheduled follow-up across 36 months. Patients either showed relapse within 36 months (alive with disease (AWD)), or remained disease-free (no evidence of disease (NED)) for the same period. Results Although the signatures did not predict recurrence, expression of the miRNAs from the CL signature decreased 1 year after surgery, and one miRNA of the signature, miR-378a-3p, almost reached significance in the NED subgroup (Wilcoxon signed-rank test: p-value = 0.078). Also, miR-335-5p from the HgA signature was higher in AWD patients before surgery (Kruskal–Wallis test: p-value = 0.019). Conclusions These data, although from a small cohort of patients, support the possible use of miRNAs as non-invasive biomarkers in liquid biopsy-based tests to identify patients at risk of relapse and to monitor them during follow-up.

Current treatment and outcomes of pediatric gastrointestinal stromal tumors (GIST): a systematic review of published studies

Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic features of pediatric GIST are not clearly defined. Clinical knowledge has been largely extrapolated from case series and adult studies. In this systematic review, we aimed to analyze the health outcome metrics of pediatric GIST. Medline and Embase databases were searched using relevant key terms. The original search retrieved 1,892 titles; 27 studies with 184 patients (68% female) were included for final review. The primary tumors were located in the stomach (165/184, 90%), small bowel (12/184, 7%), and elsewhere (7/184, 4%). Individual patient data were available in 125 cases with a median follow-up of 6.7 years. All patients underwent surgical resection, which varied from wide local excision to total gastrectomy. There were 12 deaths (10%), 65 (52%) patients were alive with no evidence of disease, and 31 cases (25%) were alive with disease. Tumor size > 5 cm, high mitotic index, and spindle morphology were predictive of mortality. Pediatric GIST has a more favorable prognosis and different characteristics versus adult tumors. There is a crucial need for international consensus and specific pediatric guidelines for the treatment of this rare tumor.

Adjuvant chemotherapy with CAV/IE for malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): An institutional analysis from Indiana University.

5026 Background: Malignant transformation of teratoma to PNET has an aggressive disease biology and generally poor outcomes when metastasis occurs. The optimal management of patients (pts) with PNET who have complete surgical extirpation is unknown. Most pts who are monitored with surveillance will relapse. We report results from pts with metastatic PNET who had complete surgical resection to NED status followed by adjuvant chemotherapy, most commonly cyclophosphamide + doxorubicin + vincristine alternating with ifosfamide + etoposide (CAV/IE) for 4 cycles. Methods: We reviewed records for pts with histologically confirmed malignant transformation of teratoma at Indiana University from 1990 to 2020. We identified 13 pts with PNET who underwent resection of metastatic disease to NED status followed by treatment with adjuvant chemotherapy, most commonly CAV/IE comprising of cyclophosphamide (1200 mg/m2), doxorubicin (75 mg/m2), and vincristine (2 mg/m2) alternating with ifosfamide (1.8 g/m2) plus etoposide (100 mg/m2). Treatment was delivered every 3 weeks for 4 cycles or until unacceptable toxicity. Results: Thirteen pts with metastatic PNET resected to NED status and received adjuvant chemotherapy were identified. Median age at diagnosis was 29 (range, 20 to 55). Primary tumor site was testis in 11 pts, retroperitoneum in 1 pt, and mediastinum in 1 pt. Metastasis site was retroperitoneal lymph nodes in 11 pts, mediastinal lymph nodes in 1 pt, and local mediastinal recurrence in 1 pt. After resection to NED status, all 13 pts were treated with adjuvant chemotherapy: 11 pts were treated with CAV/IE and 2 received etoposide-ifosfamide-cisplatin (VIP) x 2. Among the 11 pts who received CAV/IE: 3 pts received < 4 cycles due to toxicity and 8 completed 4 cycles. With a median follow-up of 16.3 months, 3 of 13 pts relapsed (23%) and 10 of 13 remained continuously disease free (77%). Of those who relapsed, median time to relapse was 9.3 months, 2 remained alive with disease at follow up and one patient died of disease progression. Conclusions: Adjuvant CAV/IE improves the outcomes of pts with malignant transformation of teratoma to PNET and who had resection of metastasis to NED status. Most pts who received adjuvant therapy remain continuously disease-free in comparison to historically high relapse rates in pts with resected PNET monitored with surveillance.

Differential Expression of Androgen Receptor in Type I and Type II Endometrial Carcinomas: A Clinicopathological Analysis and Correlation with Outcome

Objectives: Endometrial carcinomas (EC) are the most common gynecological malignancies and are conventionally divided into type I and type II due to diagnostic and prognostic considerations. Female hormone expression in EC is extensively studied; however, data about androgen receptor (AR) expression in EC are sparse. We aimed to study AR expression in different types of EC at our institute and whether it had an impact on patient outcomes. Methods: A retrospective analysis of EC cases diagnosed and treated from 2010–2019. AR immunohistochemical expression was tested in 52 EC cases (type I = 40; type II = 12). Histological typing was verified according to conventional diagnostic criteria. Only primary EC were included without neoadjuvant therapy. Histologic score was calculated as: stain intensity (graded 0–3) × positive cells percentage (graded 0–4). Level of expression was scored from 0 to 12. Results: The mean age of the selected patients was 60.3 years (range = 31–88 ± 12.6). Recurrence was detected in 11 (21.2%) patients. The outcome was 40 patients were alive without disease, eight alive with disease, three dead of disease, and one dead of other causes. About 62.5% of type I-EC and 25.0% of type II-EC were AR positive. AR expression was analyzed against different clinicopathological parameters including: type (p = 0.005), histotype (p = 0.044); grade (p = 0.035); age group (p = 0.207); menopause (p = 0.086); estrogen receptor (ER) expression (p = 0.284); atypical complex hyperplasia (p = 0.594); tumor stage (p = 0.994); tumor recurrence (p = 0.530); node status (p = 0.110); and outcome (p = 0.202). Conclusiosn: AR expression was higher in type I EC, endometrial endometrioid carcinoma histotype, and with a lower grade. AR expression was not significantly correlated with age, stage, ER, atypical hyperplasia, recurrence, node status, or outcome. Results agree with recent literature that AR expression is associated with better-differentiated EC and may be a potential hormonal therapeutic tool.

Long-term Survival Following Radiofrequency Ablation of Lung Metastases in an Elderly Patient With Calcaneal Osteosarcoma: a Case Report and Review of the Literature

Background: Lung metastases are the primary cause of death from osteosarcomas. Complete resection of lung metastases can prolong the survival. However, complete surgical resection in elderly patients is often difficult due to high risk of peri-operative complications. Radiofrequency ablation (RFA) is a minimally invasive technique to destroy tumor nodules using heat. Here, we present an elderly patient with osteosarcoma in calcaneus a scapular osteochondroma, who metachoronusly developed multiple lung metastases. Subsequently, he has been surviving a relatively long period by the use of percutaneous computed tomography (CT)-guided lung RFA against his lung metastases.Case presentation: A 74-year-old male presented with 1-year history of heel pain. Imaging analysis demonstrated a mixture of osteolytic and osteosclerotic lesions in the calcaneus with extraskeletal lesions. The histology of the biopsy specimen showed osteoid matrix with malignant spindle cells, which was diagnosed as a conventional high-grade osteosarcoma. Below-knee amputation was performed. However, 6 lung metastases were found in both lungs 1 year after surgery. During 4.5 years from the initial percutaneous CT-guided lung RFA, 18 lung metastases were treated in 8 procedures. Lung RFA was performed under moderate sedation and local anesthesia. The most frequent complication was pneumothoraxes in 3 procedures followed by pleuritis with pneumothorax in 1 procedure. Chest tube drainage was required in 2 of 8 (25%) lung RF procedures. Mean duration of hospital stay for lung RFA was 5.3 ± 2.1 days (range, 3-10 days). The patient has been alive with disease for 5.5 years after initial surgery. Conclusion: Our experience indicates that lung RFA is effective for elderly patients with lung metastases of osteosarcoma without serious complications.

How Can We Treat Vulvar Carcinoma in Pregnancy? A Systematic Review of the Literature

According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17–41 years). The tumor size range was 0.3–15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5–48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

Outcomes of Trimodal Therapy for cT2-3 Urothelial Carcinoma in a Racially Diverse Population: A Single Institution Experience in the Bronx

BACKGROUND: Radical cystectomy (RC) is the historical “gold standard” treatment for cT2-3 urothelial carcinoma (UC). However, recent evidence supports comparable outcomes of bladder preserving trimodal therapy (TMT) to RC in select patients. OBJECTIVE: To assess the oncologic outcomes of our institutional TMT experience. METHODS: We retrospectively identified all patients that received radiation therapy (RT) for cT2-3 UC from 2012 to 2018. Clinicopathologic data was then extracted from the patients’ medical records. We included patients who underwent RT with or without concurrent chemotherapy for curative intent after diagnostic TURBT, with or without re-staging TURBT. Patient clinical (age, sex, race) and pathologic/disease characteristics of bladder cancer (stage, presence of hydronephrosis, concurrent carcinoma in-situ) were collected. Primary outcomes were: response to TMT (complete response [CR], partial response [PR], progression), recurrence-free, and overall survival. We also analyzed rates of salvage cystectomy and associated disease-specific outcomes. Response was based on the first surveillance imaging, cystoscopy, or TURBT after completion of TMT. RESULTS: 24 patients underwent TMT during the study period. 29.2% of patients were black/non-hispanic, 37.5% were latino/hispanic, and 20.8% were white/non-hispanic. 58.3% of patients were female. 19 (79.2%), 3 (12.5%), and 2 (8.3%) patients experienced CR, PR and progression after TMT, respectively. At a median follow-up of 22.4 months, 19 (79.2%) patients were recurrence-free, 3 were alive with disease (12.5%), and 2 expired from other causes (8.3%; 1 with and 1 without disease present). Overall, 22 (92.7%) patients were still alive at last follow-up. No clinical variables were significant predictors of CR to TMT. CONCLUSIONS: In concordance with prior reports, TMT offers excellent tumor response rates for patients seeking definitive therapy for cT2-3 UC. Extended follow-up is needed to assess the durability of response and long-term survival after TMT.

Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer

Objective To systematically review the literature to determine the prevalence and clinical outcomes of second primary oropharyngeal squamous cell carcinoma (OPSCC). Data Sources Search strategies created with a medical librarian were implemented using multiple databases in October 2019. Review Methods The population of interest included adults age >18 years with a p16+ or human papillomavirus-positive OPSCC. The outcome was a synchronous or metachronous second primary OPSCC. Inclusion and exclusion criteria were designed to capture all study designs. In total, 685 records were identified by the search strategy. Two reviewers independently performed the review, extracted data, and performed a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A random-effects model was used for the meta-analysis. Results A total of 2470 patients with 35 second primary OPSCCs from 15 studies were identified. The pooled prevalence of second primary OPSCC was 1.4% (range, 0%-14.3%). In the random-effects model, the prevalence was estimated at 1.3% (95% CI, 0.7%-2.3%; P = .51, I2 = 52%). Of the 30 patients with treatment information, 26 (86.7%) received surgical treatment, while 4 (13.3%) underwent nonsurgical therapy. Of the 29 patients with available survival information, 22 (75.9%) had no evidence of disease at last follow-up, 5 (17.2%) ultimately died of disease, and 2 (6.9%) were alive with disease. Conclusion Overall, the rate of second primary OPSCC in patients with an index p16+ OPSCC is low, and most patients are successfully treated. Insufficient evidence currently exists to recommend routine elective tonsillectomy during surgical treatment of p16+ OPSCC.

Study of the Incidence, Clinicopathological Profile, and Management of Second Primary Tumors in Patients with Index Head and Neck Tumors

Introduction This study was performed to study the incidence and clinicopathological profile of second primary tumors (SPTs) in patients with squamous cell carcinoma of head and neck at our institute. Materials and Methods In this study, we included the data of 120 patients who developed an SPT of the upper aerodigestive tract following treatment of their index tumor (IT). Since the online data of cancer patients in our cancer registry was available from January 2005, we started the study retrospectively from that time. At our institute, Rajiv Gandhi Cancer Institute and Research Centre, the incidence was found to be 8.4%. Warren and Gates criteria were followed for defining a second tumor. Results Our study results showed an incidence of 8.4% of SPTs among patients of head and neck squamous cell carcinoma (HNSCC). The mean age of the patients was 56.47 ± 10.42 years with a male predominance. The mean period of addiction in patients was 18.48 ± 4.63 years. It was found that patients with SPT had significant history of tobacco and alcohol use. The most common location for ITs and SPT was tongue and buccal mucosa. The main modality of treatment was surgery in all patient groups. Patients were followed up at three-month intervals for the first 2 years. The SPT was diagnosed with a confirmation biopsy. Majority of patients with SPT again underwent surgery with reconstruction with either free flaps or local flaps. Recurrence after SPT treatment was seen in 16.67% cases, and primarily, it was a locoregional recurrence. Only patients with at least 6 months follow-up posttreatment of SPT were included in this study. At the end of the study, 62.5% patients were disease free, 20.83% patients were alive with disease, and 16.67% patients were dead. Some of the patients who are alive with disease developed a third primary tumor which was managed as per guidelines. Conclusion The incidence of SPTs is 8.4% in our institute. This study adds to the theory of field cancerization proposed by Slaughter et al. We found a significant history of tobacco chewing in our patients who developed SPT. The clinical significance of this study is identifying the features of SPT in patients with HNSCC and allowing for a rational follow-up schedule. The most important part of treatment although still lies with the patient by quitting use of alcohol and tobacco.