More than an Incidentaloma: The Nonreportable NIPT.

Noninvasive prenatal testing (NIPT), which utilizes a maternal blood sample to detect fetal gender and screen for fetal aneuploidy (abnormal chromosomes), is widely used in obstetrics to screen for Trisomies 21, 18, and 13. Per the literature, approximately 0.3% of pregnant woman's results are nonreportable. Reasons include low fetal fraction, insufficient DNA, vanishing twin, twin pregnancy, clonal mosaicism, and maternal neoplasia. Here, we describe a 25-year-old G2P1 pregnant woman who had two nonreportable NIPT results and subsequently was diagnosed with lymphoma. We discuss the importance of clinical exam in correlation with the results to offer comprehensive evaluation of the patient with a nonreportable finding, given malignancy occurs in 1/1000 pregnant women. This report overviews proposed management guidelines for pregnant women with a nonreportable result and helps to address discomfort the treating physician may feel in discussing this result with their patient.

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report.

PURPOSE: The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS: Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS: Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION: While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

Comparison of Three Groups of Patients Having Low Dose Rate Prostate Brachytherapy: Prostate-Specific Antigen Failure and Overall Survival.

Purpose To examine dosimetric and clinical outcomes for Cs-131 radioactive seed implant compared to Pd-103 and I-125.  Background/Significance Cs-131 is a novel isotope with relatively short half-life (9.7 days) that may have clinical advantages in seed implant treatments of prostate cancers. There may be a shorter duration of symptoms and increased PSA control rates. Methods We performed a retrospective study in which clinical and dosimetric outcomes were compared for 186 prostate implants performed over a ten-year time period at three different Ascension hospitals. Isotopes that were used included Cs-131 (n=66; half-life 9.7 days), I-125 (n=60; half-life 60 days), and Pd-103 (n=60; half-life 17 days) Results The implants used standard radiation dosages. These were 145 Gy for I-125 alone or 109 Gy when combined with external beam radiation. In the case of Cs-131 used alone, the dose was 115 Gy or 85 Gy when combined with an external beam. For Pd-103, 125 Gy was used for monotherapy and 90 Gy when combined with an external beam. The Cs-131 dosimetry was found to be similar to I-125 and Pd-103 on a quantitative basis. However, there was better homogeneity, and the delivered activity per seed and the number of seeds employed were greater compared to other isotopes. We compared the corrected total source strengths (i.e. normalized to sample mean values) and were able to demonstrate similar distributions for the three isotopes. Dosimetric analysis also suggested there was superior homogeneity with Cs-131. The median PSA value at 60 months was 0.11 ng/ml. There were only a few PSA failures in the three groups of cases, nonetheless, the Cs-131 had the fewest.  Conclusions One attractive option for men with early-stage prostate cancer is interstitial brachytherapy. The use of the shorter-acting Cs-131 isotope may be expected to have dose-related side effects that resolve more rapidly. This series suggests a trend for improved PSA control outcomes for Cs-131 patients compared with I-125 and Pd-103.

Rare tumors: Retinoblastoma, nasopharyngeal cancer, and adrenocorticoid tumors.

The role of surgery, chemotherapy, and radiation therapy for retinoblastoma has evolved considerably over the years with the efficacy of intraarterial chemotherapy and the high incidence of secondary malignant neoplasms following radiation therapy. The use of spot scanning intensity-modulated proton therapy may reduce the risk of secondary malignancies. For pediatric nasopharyngeal carcinoma, the current standard of care is induction chemotherapy followed by chemoradiation therapy. For adrenocortical carcinoma, the mainstay of treatment is surgery and chemotherapy. The role of radiation therapy remains to be defined.

Management of Prostate Cancer During COVID-19 Pandemic: Perspective From Urologists and Radiation Oncologists in COVID Dense Metro Detroit.

Objective To survey Urologists and Radiation Oncologists in Metropolitan Detroit regarding practice patterns in managing non-metastatic prostate cancer during the pandemic.  Methods An online survey was created to capture the perspective of the impact the COVID-19 restrictions have on the management of prostate cancer by Urologists and Radiation Oncologists in the Detroit Metropolitan area.  Results While most physicians felt that their facilities had adequate quantities of personal protective equipment (PPE), one in four offices reported that they did not have sufficient access to PPE. Urologists surveyed indicated that most of the low risk prostate cancer surgeries were cancelled and 56.2% had half or more of intermediate and high risk disease prostatectomies cancelled as well. Treatment options were then shifted towards either temporary surveillance or hormone therapy. Radiation Oncologists indicated that prostate cancer patients ready to start treatment were mostly delayed with temporary surveillance or hormone therapy depending on risk category (60% indicated they delayed low risk and favorable intermediate risk cases, 56% unfavorable intermediate risk cases, and 44% high risk cases). More than 80% of patients already undergoing treatment continued radiation.  Conclusion In the setting of this pandemic, the management of prostate cancer has shifted to a much more conservative approach. While the response to the crisis has not been uniform, the majority of the practitioners followed newly established guidelines. The long-term outcomes of delays and deviations from standard treatment approaches will remain to be seen.

The Children's Oncology Group Radiation Oncology Discipline: 15 Years of Contributions to the Treatment of Childhood Cancer.

PURPOSE: Our aim was to review the advances in radiation therapy for the management of pediatric cancers made by the Children's Oncology Group (COG) radiation oncology discipline since its inception in 2000. METHODS AND MATERIALS: The various radiation oncology disease site leaders reviewed the contributions and advances in pediatric oncology made through the work of the COG. They have presented outcomes of relevant studies and summarized current treatment policies developed by consensus from experts in the field. RESULTS: The indications and techniques for pediatric radiation therapy have evolved considerably over the years for virtually all pediatric tumor types, resulting in improved cure rates together with the potential for decreased treatment-related morbidity and mortality. CONCLUSIONS: The COG radiation oncology discipline has made significant contributions toward the treatment of childhood cancer. Our discipline is committed to continuing research to refine and modernize the use of radiation therapy in current and future protocols with the goal of further improving the cure rates and quality of life of children with cancer.

Abscopal Effect after Radiosurgery for Solitary Brain Metastasis from Non-small Cell Lung Cancer.

The abscopal effect is a phenomenon relating to the treatment of metastatic cancer in which localized irradiation to a tumor concurrently causes shrinkage of tumors distant from the area of treatment. Localized radiotherapy is thought to cause anti-tumor immunologic responses that lead to regression and remission of cancers distant to the initial location of treatment. We present a 47-year-old male with brain metastasis from non-small cell lung cancer (NSCLC) who went into remission following stereotactic radiosurgery treatment to a brain lesion, in the absence of systemic treatment. We discuss the novelty of this case and its importance to future research on the abscopal effect. Though it is difficult to distinguish the abscopal effect from spontaneous remission of non-targeted cancer, this report sheds insight on the potential for improving treatment for the leading cause of cancer death worldwide.

Radiation and depression associated with complications of tissue expander reconstruction.

PURPOSE: Rates of implant failure, wound healing delay, and infection are higher in patients having radiation therapy (RT) after tissue expander (TE) and permanent implant reconstruction. We investigated pretreatment risk factors for TE implant complications. PATIENTS AND METHODS: 127 breast cancer patients had TE reconstruction and radiation. For 85 cases of bilateral TE reconstruction, the non-irradiated breast provided an internal control. Comparison of differences in means for continuous variables used analysis of variance, then multiple pairwise comparisons with Bonferroni correction of p value. RESULTS: Mean age was 53 ± 10.1 years with 14.6% African-American. Twelve (9.4%) were BRCA positive (9 BRCA1, 4 BRCA2, 1 Both). Complications were: Grade 0 (no complication; 43.9%), Grade 1 (tightness and/or drifting of implant or Baker Grade II capsular contracture; 30.9%), Grade 2 (infection, hypertrophic scarring, or incisional necrosis; 9.8%), Grade 3 (Baker Grade III capsular contracture, wound dehiscence, or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of implant, or Baker Grade IV capsular contracture; 9.8%). 15.3% (19 cases) experienced Grade 3 or 4 complication and 9.8% (12 cases) had Grade 4 complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3-4 complications. For BMI, there was no significant difference by category as defined by the CDC (p = 0.91). Patients with depression were more likely to experience Grade 3 or 4 complication (29.4 vs 13.2%; p = 0.01). Using multiple logistic regression to predict the probability of a Grade 3 or 4 complications in patients with depression were found to be 4.2 times more likely to have a Grade 3 or 4 complication (OR = 4.2, p = 0.03). CONCLUSIONS: Higher rates of TE reconstruction complications are expected in patients receiving radiotherapy. An unexpected finding was that patients reporting medical history of depression showed statistically significant increase in complication rates.

Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.

PURPOSE: This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. PATIENTS AND METHODS: Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. RESULTS: The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. CONCLUSION: Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies.

A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893.

BACKGROUND: The aims of this study were to determine the feasibility of the combination of low dose, anti-angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data. PROCEDURES: Patients with metastatic ES were eligible. Therapy consisted of alternating cycles of ifosfamide-etoposide, and vincristine, doxorubicin, cyclophosphamide. Vinblastine and celecoxib were concomitantly administered. Surgical, radiotherapeutic, or combination local control therapy was given per institutional preference. RESULTS: Thirty-five eligible patients were enrolled. Ninety percent received at least 75% of planned vinblastine/celecoxib doses. There was no excess of neurologic, infectious, hemorrhagic, or cardiovascular toxicities. However, 7 of 21 patients who received pulmonary irradiation prior to experiencing pulmonary toxicity did develop grade 2 or greater pulmonary toxicity, including two deaths of apparent radiation pneumonitis. Fourteen of 16 patients with pelvic disease received local irradiation. Hemorrhagic cystitis developed in six patients, five of whom had received pelvic irradiation. The overall 24-month event free survival was 35% (19-51%); 71% (26-92%) for the seven with isolated pulmonary metastases, 26% (10-45%) for all others. CONCLUSION: The combination of vinblastine/celecoxib metronomic therapy with standard ES treatment was feasible according to the protocol definitions. However, excess toxicity in irradiated areas was noted and limits the usefulness of this protocol. The 24-month EFS for those with isolated pulmonary metastases is better than historical controls, although the number of patient number is small, follow up short and we are lacking contemporaneous controls.

Three-dimensional visualization and dosimetry of stranded source migration following prostate seed implant.

PURPOSE: Computed tomographic (CT) imaging was used to determine the displacement of stranded seeds between day 0 and day 30 following prostate seed implants. Post-plan dosimetry was used to assess the dosimetric consequence of strand displacement. METHODS AND MATERIALS: Between March 2006 and December 2009, 86 prostate seed implant patients had day 0 and day 30 post-plan CT imaging. Migrated strands were first identified by inspection of day 0 and day 30 scans. The exact distance of displacement was measured using 3-dimensional fusion software. Post-plan dosimetric analysis was performed using CMS software. RESULTS: Of the 1550 strands placed, 23 strands exhibited substantial movement and these displacements occurred in 21 of the 86 cases. The measured distance of strand movement ranged from 0.31 cm to 3.44 cm, with mean displacement of 2.75 cm. Of the displaced strands, 15 strands moved away from the implant center while 8 strands moved toward the implant center. A comparison of changes in dosimetric parameters between day 0 and day 30 revealed expected increases in D90 related to resolution of prostate edema. When cases of strand displacement were compared with cases without displacement, there were no differences in D90 or V100 at day 0. At day 30, however, statistically significant decreases in D90 (96.8% vs 89.5%; P = .0061) and V100 (85.9% vs 82.2%; P = .046) were noted for cases with strand displacement. When the data were analyzed by looking at the change in dosimetric parameters over time for each individual case (eg, comparing the difference in D90 from day 0 to day 30 per patient) there was a trend toward decrease in D90 with displacement of the strands but this did not achieve statistical significance (P = .09). CONCLUSIONS: Stranded seeds show unexpected spatial instability in the craniocaudal dimension. Strand displacement may occur in approximately 1.5% of stranded sources placed and about 25% of cases. One may expect mean decreases in D90 and V100 of about 7% and 3%, respectively, among cases exhibiting strand migration in the first month following seed implant. Resolution of prostate edema during the same time period accounts for an approximately 30% increase in D90 and V100.

Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976: follow-up of a Children's Oncology Group cohort.

BACKGROUND: The growing number of individuals surviving childhood cancer has increased the awareness of adverse long-term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs). METHODS: The authors describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors who were treated on legacy Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005. This retrospective cohort study included 2842 patients: 1686 who were treated for osteosarcoma (OS) and 1156 who were treated for Ewing sarcoma (ES). RESULTS: The cohort included 56% boys/young men and 44% girls/young women, and the median age at primary diagnosis was 13 years. The median length of follow-up was 6.1 years (range, 0-20.9 years). In this analysis, 64% of patients were alive. Seventeen patients with solid organ SMN were identified. The standardized incidence ratio was 2.9 (95% confidence interval [CI], 1.4-5.4) for patients who were treated for OS and 5.0 (95% CI, 2.6-9.4) for patients who were treated for ES. The median time from diagnosis to development of solid SMN was 7 years (range, 1-13 years). The 10-year cumulative incidence of solid organ SMN for the entire cohort was 1.4% (95%CI 0.6%-2%). CONCLUSIONS: The magnitude of risk of solid SMNs was modest after treatment for malignant bone tumors. However, radiation-related solid SMNs will increase with longer follow-up. Because nearly 33% of patients die from their disease, recurrence remains the most significant problem. The development of improved therapies with fewer long-term consequences is paramount. Follow-up should focus on monitoring for both recurrence of primary malignancies and development of SMNs.

Pathological distribution of positive lymph nodes in patients with clinically and radiologically N0 oropharyngeal carcinoma: implications for IMRT treatment planning.

BACKGROUND: We identified involved lymph node groups in patients with oropharyngeal carcinoma and radiologically N0 disease, aiming to define the clinical target volume, and to assess the negative predictive value of CT neck and correlate it to the tumor site, stage, and grade. METHODS AND MATERIALS: Between 1988 and 2000, we evaluated 53 patients who satisfied all of the following criteria: 1) oropharyngeal carcinoma diagnosis; 2) NO stage based on CT; 3) no prior treatment; and 4) primary surgical resection including ipsi-lateral neck dissection. The pathology reports were reviewed to identify the exact site of lymph node involvement. RESULTS: Twenty patients (37.7%) were found to have pathologically positive lymph nodes, yielding a negative predictive value of 62.3% for CT neck. Node levels II, III, and IV were the most commonly involved (26%, 17%, and 11% of all patients, respectively). Fifty percent of patients with T3 and T4 tumors had positive lymph nodes versus 20% of patients with T1 and T2 (P = 0.036). Tumor grade and site were insignificant (P > 0.05). DISCUSSION: Ipsilateral neck levels II-IV should be included during elective nodal irradiation in patients with N0-stage oropharyngeal carcinoma, regardless of the primary tumor site, stage, and grade.

Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: analysis of surveillance, epidemiology, and end results data.

PURPOSE: Noninvasive lesions involving the lobules of the breast are increasingly diagnosed as incidental microscopic findings at the time of lumpectomy or core-needle biopsy. We investigated the incidence rates of invasive breast cancer (IBC) after a diagnosis of lobular carcinoma-in-situ (LCIS) by using Surveillance, Epidemiology, and End Results (SEER) data. PATIENTS AND METHODS: Patients (N = 4,853) having a diagnosis of primary LCIS in the time period of 1973 to 1998 were identified using the SEER Public Use CD-ROM data. The database was then searched for patients with subsequent primary IBC occurrences (n = 350). The clinical and pathologic characteristics of patients with subsequent primary IBCs were compared with the characteristics of patients with primary IBCs attained during the same time period (N = 255,114). RESULTS: The incidence of IBC increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC at 10 years. IBCs detected after partial mastectomy occurred in either breast (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs were contralateral (94.7%). IBCs occurring after LCIS more often represented invasive lobular histology (23.1%) compared with primary IBCs (6.5%). The standardized incidence ratio (the ratio of observed to expected cases) for developing IBC was 2.4 (95% CI, 2.1 to 2.6) adjusted for age and year of diagnosis. CONCLUSION: LCIS is associated with increased risk of subsequent invasive disease, with equal predisposition in either breast. The minimum risk of developing IBC after LCIS is 7.1% at 10 years.

A population-based study of racial and ethnic differences in survival among women with invasive cervical cancer: analysis of Surveillance, Epidemiology, and End Results data.

OBJECTIVE: The incidence of cervical cancer is higher in Hispanic than in non-Hispanic or African American women in the United States, but few studies have examined differences in survival between these groups. The objective of this study was to examine racial/ethnic differences in survival after diagnosis with invasive cervical cancer in a population-based sample of patients while adjusting for patient and tumor characteristics and treatment types. METHODS: We identified 7267 women (4431 non-Hispanic Caucasians, 1830 Hispanic Caucasians, and 1006 non-Hispanic African Americans) diagnosed with primary invasive cervical cancer from 1992 to 1996 (with follow-up through 2000) from the Surveillance, Epidemiology and End Results (SEER) Program. Kaplan-Meier and Cox proportional hazards survival methods were used to assess differences in survival by race/ethnicity. RESULTS: After adjusting for age at diagnosis, histology, stage, first course of cancer-directed treatment (surgery and radiation therapy), and SEER registry, Hispanic Caucasian women were at 26% decreased risk of death from any cause (hazard ratio (HR) = 0.74, 95% confidence interval (CI): 0.66-0.83) and non-Hispanic African American women were at 19% increased risk of death (HR = 1.19, 95% CI: 1.06-1.33) compared to non-Hispanic Caucasian women over the follow-up period. CONCLUSION: Analysis of population-based SEER data indicates significant survival differences by race/ethnicity for women with invasive cervical cancer. Hispanic Caucasian women in SEER had improved survival compared to non-Hispanic Caucasian or non-Hispanic African American women.

Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence.

The standardized incidence ratios (SIR) and cumulative incidence rates were determined for developing second malignant neoplasms (SMNs) after primary central nervous system (CNS) malignancies occurring during childhood using registry data. A total of 4553 cases of primary CNS malignancies were identified. Forty-six cases developed SMNs, 19 occurring in a previously radiated field. The SIRs of developing second malignant neoplasms were 6.3 and 3.1 for those cases receiving and not receiving radiation therapy, respectively. The 20-year cumulative incidences for developing SMNs were 3.3 and 1.2% for cases receiving and not receiving radiation therapy, respectively. Children surviving CNS malignancies have an increased susceptibility for SMNs.

Osteosarcoma as a second malignant neoplasm.

PURPOSE: The aim of this study is to compare primary and secondary osteosarcomas using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. METHODS: Osteosarcoma cases were identified in the SEER Cancer Incidence Public-Use Database, 1973-96 (1,511 primary and 133 secondary osteosarcomas). Secondary osteosarcomas were further classified as occurring within or outside the previously irradiated field. Comparisons among groups were performed by nominal logistic regression. Survival analyses were performed using Kaplan-Meir and proportional hazards regression. RESULTS: Secondary osteosarcomas were more likely to have a non-extremity primary site and an older age at diagnosis (>40 years) (<0.0001 for both). Secondary osteosarcoma cases continued to be more likely to have a non-extremity site when excluding those occurring within the radiation field. Five-year overall survival was 50% lower for secondary osteosarcomas for both extremity and non-extremity sites. Primary malignancies associated with secondary osteosarcomas included 14 lymphomas/leukemias, six sarcomas, 54 carcinomas, and seven other cancers. Secondary osteosarcomas occurring within a field of radiation were more likely to occur at a younger age, have a malignancy with a primary morphology other than carcinoma, a non-limb site, and a longer duration between their primary malignant neoplasms and the development of osteosarcoma. No difference in the overall survival was noted between secondary osteosarcomas occurring within an irradiated field and those that did not. CONCLUSIONS: Secondary osteosarcomas are associated with carcinomas especially in the elderly. Although a 50% decreased 5-year survival was observed for secondary osteosarcomas in this study, this might not reflect the current outcomes with more aggressive therapy.