Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

Treatment of intermediate-risk prostate cancer with Cs-131: Long-term results from a single institution.

PURPOSE: To evaluate our institutional outcomes utilizing Cs-131 prostate brachytherapy (PB) for the intermediate-risk (IR) group of prostate cancer patients. METHODS AND MATERIALS: We reviewed a prospectively collected database of men treated with Cs-131 PB between 2006 and 2019. Patients with less than 24-months follow-up were excluded. Patients were classified as IR if they had one of the following factors: Gleason Score 7, prostate specific antigen >10 but <20 ng/mL, or T2b-c on clinical exam. We defined unfavorable-IR (UIR) as having either Grade Group 3, >1 IR factors, or ≥50% positive core biopsies. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical freedom from disease (BFD). RESULTS: A total of 335 patients with a median follow-up of 70.1 months (IQR 48.3-106.3 months) were identified. Androgen deprivation therapy (ADT) was used in 7.2% of patients. Favorable-IR (FIR) patients were commonly treated with PB alone (91.8%). FIR patients who underwent PB alone had a 5-year BFD of 98.1%. UIR patients were commonly treated with external beam radiotherapy plus PB (61.2%). These patients had 5-year BFD of 91.1%. The 5-year BFD for UIR patients treated without ADT was 90.9%, whereas it was 95.0% among UIR patients treated with ADT (log-rank p = 0.83). CONCLUSIONS: FIR patients have excellent outcomes when treated with PB alone. External beam radiotherapy plus PB is a reasonable treatment approach for UIR patients. Future studies may elucidate which IR patients would benefit from treatment intensification.

Intraprostatic calcification and biochemical recurrence in men treated with cesium-131 prostate brachytherapy.

PURPOSE: Baseline intraprostatic calcification (IC) has been shown to be associated with a higher rate of biochemical recurrence (BCR) in men treated with iodine-125 prostate brachytherapy (PB). We evaluated this association in a cohort of men treated with cesium-131 PB. METHODS AND MATERIALS: We retrospectively reviewed the charts of all low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- external beam radiotherapy (EBRT) at our institution from 2/2011 to 7/2018. Patients with < 24 months of follow up or those who received androgen deprivation therapy were excluded. Baseline IC status (defined as one or more ICs ≥ 5 mm) was determined on post-PB CT scans. Cox analysis was used to assess predictors of BCR and Kaplan-Meier survival curves were calculated. RESULTS: Two hundred and sixteen low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1-111.4). Overall, 76 (35.2%) patients had baseline IC and 140 (64.8%) did not. Baseline disease characteristics did not differ significantly between groups. On univariate Cox analysis, only risk group (p = 0.047) and initial PSA (p = 0.016) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with versus without baseline IC was 97.7% versus 93.8% (p = 0.405), respectively. CONCLUSIONS: In a cohort of low- and intermediate-risk prostate cancer patients treated with cesium-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

Utility of Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer in the MRI Screening Era.

BACKGROUND: Conflicting data exists regarding the benefit of prophylactic cranial irradiation (PCI) in patients with extensive-stage small-cell lung cancer (ES-SCLC). We sought to retrospectively review outcomes of patients within our network with ES-SCLC treated with and without PCI between 2009 and 2020. METHODS: Endpoints assessed using the Kaplan-Meier estimator were overall survival (OS), freedom from death with uncontrolled intracranial disease (UI-DFS), brain metastasis-free survival (BMFS), and symptomatic BMFS (SBMFS). Log-rank test was performed for univariate comparison of outcomes, with Cox regression performed for univariate and multivariable analysis of OS and UI-DFS. RESULTS: Some 250 patients were determined to be eligible for PCI based on any response to upfront chemotherapy, with 46 patients excluded owing to lack of negative staging brain magnetic resonance imaging (MRI). Brain MRI was performed both at diagnosis and near completion of chemotherapy in 108 patients, with brain metastases identified near completion of chemotherapy in 17 patients (15.7%), excluding them from further analysis. Median OS in remaining eligible 187 patients was 9.0 months, with 2-year Kaplan-Meier estimate of OS of 21.9%. PCI was associated with improved UI-DFS, BMFS, and SBMFS. However, PCI was not associated with improved OS in the entire cohort or the propensity matched cohort. CONCLUSION: Our study suggests screening with MRI following chemotherapy is important because of the identification of unsuspected brain metastases in nearly 16% of patients with response to chemotherapy. PCI is associated with reduction in brain metastases, without a demonstrable impact on OS in the era of MRI screening.

Do air gaps with image-guided vaginal cuff brachytherapy impact failure rates in patients with high-intermediate risk FIGO Stage I endometrial cancer?

PURPOSE: The aim of this study was to assess the impact of air gaps at the cylinder surface on the rate of vaginal cuff failure (VCF) after image-guided adjuvant vaginal cuff brachytherapy (VCBT) in the treatment of high-intermediate risk (HIR) FIGO (Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics)) Stage I endometrial cancer. METHODS AND MATERIALS: A retrospective review of patients treated with image-guided VCBT from 2009 to 2016 for HIR FIGO Stage I endometrial cancer was performed. Air gaps present at the applicator surface on the first postinsertion CT were contoured. Vaginal cuff failure-free survival (VCFFS) was measured from the first fraction of VCBT to VCF. RESULTS: A total of 234 patients were identified. Air gaps were present on the first postinsertion CT scan in 82% of patients. The median number of air gaps was 2 (interquartile range [IQR] 1-3), median depth of the largest air gap was 2.7 mm (IQR 2.1-3.4 mm), and the median cumulative volume of air gaps was less than 0.1 cm3 (range < 0.1-0.7 cm3). At a median followup of 56 months (IQR 41-69), 12 patients (5%) experienced VCF, of which 4 had isolated VCF and 8 had synchronous pelvic or distant failure. Five-year VCFFS and isolated VCFFS were 96% (95% confidence interval 93-98%) and 98% (95% confidence interval 96-100%), respectively. On univariate analysis, no factors, including the presence, number, maximum depth, or cumulative volume of air gaps, were predictive for VCFFS. CONCLUSIONS: In this population, VCFFS remained high despite most patients having air gaps present on postinsertion CT scan.

Long term outcomes with linear accelerator stereotactic radiosurgery for treatment of jugulotympanic paragangliomas.

BACKGROUND: Data supporting linear accelerator (linac) stereotactic radiosurgery (SRS) for jugulotympanic paragangliomas (JTPs) come from small series with minimal follow-up. Herein, we report a large series of JTPs with extended follow-up after frameless linac-based SRS. METHODS: JTPs treated with linac-based SRS from 2002 to 2019 with 1+ follow-up image were reviewed for treatment failure (radiographic or clinical progression, or persistent symptoms after SRS requiring intervention) and late toxicities (CTCAE v5.0). RESULTS: Forty JTPs were identified; 30 were treated with a multifraction regimen. Median clinical and radiographic follow-up was 79.7 (interquartile range [IQR] 31.7-156.9) and 54.4 months (IQR 17.9-105.1), respectively, with a median 4.5 follow-up scans (IQR 2-9). Seven-year progression-free survival (PFS) was 97.0% (95% confidence interval 91.1%-100.0%). PFS was similar between single- and multifraction regimens (log rank P = .99). Toxicity was seen in 7.7% (no grade III). CONCLUSIONS: With extended clinical and radiographic follow-up, frameless linac-based SRS provides excellent local control with mild toxicity <8%.

Ureteral stenosis after 3D MRI-based brachytherapy for cervical cancer - Have we identified all the risk factors?

BACKGROUND AND PURPOSE: Ureteral stenosis (US) is a known complication from image-guided brachytherapy (IGBT); however, no dosimetric parameter has been associated with ureteral toxicity. We aimed to report the rate of late grade ≥3 US after MRI-based IGBT, and to identify clinical factors and dosimetric parameters predictive for US. MATERIALS AND METHODS: A retrospective review was performed on all cervical cancer patients treated with MRI-based IGBT between 2007 and 2017. Late grade ≥3 US was recorded according to CTCAE 4.03. The minimum dose to the maximally irradiated 0.1 cm3 of ureter (D0.1cm3) was extracted from dose-volume histograms. Binary logistic regression was performed to identify predictors of late grade ≥3 US. RESULTS: 242 patients with a median follow-up of 35.8 months (IQR, 19.2-60.8) were identified. Late grade ≥3 US occurred in 18 patients, and the actuarial 3-year rate was 7.3% (95% CI 3.3-11.3). After excluding patients with pre-existing hydronephrosis, late grade ≥3 US occurred in 11 patients with an actuarial 3-year rate of 4.4% (95% CI 1.7-7.1). Ureters with D0.1cm3 ≥77 Gy had a 28.6% incidence of late grade ≥3 US compared to 7.5% in those with D0.1cm3 <77 Gy (OR 2.39; 95% CI 1.23-4.65; p = 0.01). The incidence of late grade ≥3 US was 33.3%, and 40.0% for ureters receiving ≥85 and ≥90 Gy, to D0.1cm3, respectively. CONCLUSION: After MRI-based IGBT, there is an estimated 4.4% risk of developing late grade ≥3 US among patients without pre-existing hydronephrosis. Ureteral dose ≥77 Gy to D0.1cm3 correlates with development of late grade ≥3 US.

Treatment selection and survival outcomes in Early-Stage peripheral T-Cell lymphomas: does anaplastic lymphoma kinase mutation impact the benefit of consolidative radiotherapy?

The role of consolidative radiotherapy (RT) is less substantiated in uncommon peripheral T-cell lymphomas (PTCLs). Anaplastic lymphoma kinase (ALK) mutation sub-categorizes PTCLs, with ALK (+) having a distinctly favorable prognosis. We aimed to use the National Cancer Database to examine the potential role of RT in PTCLs and if ALK mutation can be used to predict the benefit of consolidative RT after multi-agent chemotherapy (combined modality therapy). We identified 3670 stage I-II PTCL patients treated with multi-agent chemotherapy alone or combined modality therapy (CMT) between 1998-2012. After adjusting for immortal-time and indication bias, CMT was associated with better OS than multi-agent chemotherapy alone for ALK (-) patients (HR 0.69, 95% CI 0.52-0.92, p = .01); no significant difference was noted for ALK (+) (HR 1.03, 95% CI 0.75-1.41, p = .85). CMT is associated with improved OS for ALK (-) PTCLs; while no such benefit was seen for the ALK (+) subgroup.

Patterns of Failure After Adjuvant Stereotactic Body Radiation Therapy for Pancreatic Cancer With Close or Positive Margins.

PURPOSE: There is no consensus on treatment volumes for adjuvant stereotactic body radiation therapy (SBRT) for pancreatic cancer. Herein, we report patterns of failure after pancreatic SBRT for close/positive margins, which may inform target volume design. METHODS AND MATERIALS: An institutional review board-approved retrospective review of patients with pancreatic adenocarcinoma treated with adjuvant SBRT for close/positive margins from 2009 to 2018 was conducted. Patterns of failure were defined as local (LF) within the tumor bed, regional (RF) within lymph nodes or anastomoses, or distant (DF). The cumulative incidence of locoregional failure was calculated using the cumulative incidence function accounting for the competing risk of death. LFs were mapped to the planning target volume (PTV) and classified as in-field (completely within the PTV), marginal (partially within the PTV), or out-of-field (completely outside the PTV). The location of LFs was compared with the Radiation Therapy Oncology Group 0848 contouring atlas to determine whether standard postoperative radiation therapy volumes would have included the LF. RESULTS: Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins. Most (81.6%) received 36 Gy in 3 fractions, with a median PTV volume of 17.8 cc (interquartile range, 12.1-25.6). With a median follow-up of 17.0 months (interquartile range, 7.3-28.4), crude rates of first isolated LF, isolated RF, and DF +/- LF or RF were 9.2%, 6.6%, and 56.6%, respectively. Two-year cumulative incidences of LF, RF, locoregional failure, and DF were 34.9%, 30.8%, 49.2%, and 60.4%, respectively. Of 28 reviewable LFs, 21.4% were in-field while the remainder were completely outside (60.7%) or partially outside (17.9%) the PTV. Most LFs (92.9%) would have been encompassed by the Radiation Therapy Oncology Group consensus target volumes. CONCLUSIONS: After adjuvant pancreatic SBRT for close/positive margins, the majority of LFs were outside the PTV but within contemporary target volumes for conventional radiation therapy.

External validation of life expectancy prognostic models in patients evaluated for palliative radiotherapy at the end-of-life.

BACKGROUND: The TEACHH and Chow models were developed to predict life expectancy (LE) in patients evaluated for palliative radiotherapy (PRT). We sought to validate the TEACHH and Chow models in patients who died within 90 days of PRT consultation. METHODS: A retrospective review was conducted on patients evaluated for PRT from 2017 to 2019 who died within 90 days of consultation. Data were collected for the TEACHH and Chow models; one point was assigned for each adverse factor. TEACHH model included: primary site of disease, ECOG performance status, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases; patients with 0-1, 2-4, and 5-6 adverse factors were categorized into groups (A, B, and C). The Chow model included non-breast primary, site of metastases other than bone only, and KPS; patients with 0-1, 2, or 3 adverse factors were categorized into groups (I, II, and III). RESULTS: A total of 505 patients with a median overall survival of 2.1 months (IQR: 0.7-2.6) were identified. Based on the TEACHH model, 10 (2.0%), 387 (76.6%), and 108 (21.4%) patients were predicted to live >1 year, >3 months to ≤1 year, and ≤3 months, respectively. Utilizing the Chow model, 108 (21.4%), 250 (49.5%), and 147 (29.1%) patients were expected to live 15.0, 6.5, and 2.3 months, respectively. CONCLUSION: Neither the TEACHH nor Chow model correctly predict prognosis in a patient population with a survival <3 months. A better predictive tool is required to identify patients with short LE.

Physician-Predicted Prognosis and Palliative Radiotherapy Treatment Utilization at the End of Life: An Audit of a Large Cancer Center Network.

CONTEXT: At our institution, clinical pathways capture physicians' prognostication of patients being evaluated for palliative radiotherapy. We hypothesize a low utilization rate of long-course radiotherapy (LCRT) and stereotactic ablative radiotherapy (SAbR) among patients seen at the end of life, especially those with physician-predicted poor prognosis. OBJECTIVE: To analyze utilization rates and predictors of LCRT and SAbR at the end of life. METHODS: A retrospective review was conducted on patients who were evaluated for palliative radiotherapy between January 2017 and August 2019 and died within 90 days of consultation. Binary logistic regression was used to identify predictors for utilization of LCRT (≥10 fractions) and SAbR. RESULTS: A total of 1608 patients were identified, of which 1038 patients (64.6%) were predicted to die within a year. Six hundred ninety-three patients (66.8%) out of 1038 were prescribed LCRT or SAbR. On a multivariate analysis, patients were less likely to be prescribed LCRT if treated at an academic site (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.23-0.39; P < 0.01) and treated for bone metastases (OR, 0.08; 95% CI, 0.05-0.11; P < 0.01) or other nonbrain/nonbone metastases (OR, 0.19; 95% CI, 0.13-0.30; P < 0.01). SAbR was less likely to be prescribed among patients predicted to die within a year (OR, 0.09; 95% CI, 0.06-0.16; P < 0.01), treated for bone metastases (OR, 0.13; 95% CI, 0.07-0.22; P < 0.01), with poor performance status (OR, 0.51; 95% CI, 0.31-0.85; P = 0.01), and with a breast primary (OR, 0.35; 95% CI, 0.15-0.82; P = 0.02). CONCLUSION: Although most patients were predicted to have a limited prognosis, LCRT and SAbR were commonly prescribed at the end of life.

Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology.

BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival. METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed. RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM. CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.

Lag Time Between Evidence and Guidelines: Can Clinical Pathways Bridge the Gap?

PURPOSE:: The 2018 American Society for Radiation Oncology guidelines state that hypofractionated whole-breast irradiation (HF-WBI) may be used for early-stage breast cancer regardless of age, although evidence to support this became available years ago. Before guideline publication, we sought to change the practice pattern within an integrated, comprehensive radiation oncology network using clinical pathways. METHODS:: The breast clinical pathway was amended in January 2016 to allow HF-WBI as a pathway-concordant option for women younger than 50 years of age. In December 2016, the pathway was amended to mandate HF-WBI as the only pathway-concordant option. Women younger than 50 years of age treated for stage 0 to IIA breast cancer, without irradiation of regional nodes, were included. Potential predictors of hypofractionation use were analyzed using binary logistic regression. RESULTS:: We identified 305 patients treated between 2013 and 2017. From 2013 to December 2015, HF-WBI use was 4.2%. After the first and second amendments, use increased to 53.1% ( P < .001) and 96.5% ( P < .001), respectively. Before amendment 1, there was no difference in use of hypofractionation at academic (2.6%) versus community (4.7%) sites ( P = .568). After amendment 1, academic practices were more likely to use hypofractionation (72.0% v 44.6%; P = .026). After amendment 2, there was, again, no difference between academic (100.0%) and community (95.3%) practices ( P = .999). CONCLUSION:: With implementation of a clinical pathway that mandated use of HF-WBI regardless of age, HF-WBI use for women younger than 50 years of age rapidly increased from 4.2% to greater than 95%. Clinical pathways effectively standardize patterns of care to reflect the most up-to-date clinical evidence, independently of guideline publication.

High dose intravenous vitamin c treatment in a patient with lung cancer: A case report.

Lung cancer is one of the most common cancers in both men and women. According to Dr. Abram Hoffer, patients with a better nutritional plan and daily Vitamin C supplementation improved their life quality. In this case report we present the case of a 56-year-old Hispanic male patient diagnosed with lung cancer on 2012. After undergoing surgery and chemotherapy, he started a high dose intravenous Vitamin C protocol on December 2013. The treatment continued until June 2015, when the patient decided to stop the treatment. A maximum of 75 gr of Vitamin C in 1,000 cc lactated Ringer's was given three times a week in a period over a year and a half. Patient's CEA levels continued to be within normal levels while high doses of Vitamin C infusions were given. Many case reports suggest that patients with lung cancer that received high doses of intravenous Vitamin C can live up to 10 years. A level of Vitamin C in plasma above 400 mg/dL is toxic to tumor cells, this can be achieved with periodic Vitamin C infusions. Our case support that the usage of high doses of IV Vitamin C can be effective in the treatment of patients with cancer without secondary effects.

Difficult Diagnosis between B Cell Lymphoma and Classical Hodgkin's Lymphoma.

Although primary mediastinal large B-cell lymphoma and classic Hodgkin lymphoma of nodular sclerosis type are distinct disease, they share several clinical characteristics and biologic features. However, there are mediastinal lymphomas that not fit in either category. These types of lymphomas are recognized as mediastinal gray zone lymphomas. Gray zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical, or genetic reasons. In this report, we present a case of a 22 year-old-Hispanic-female diagnosed with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin lymphoma.