Bloom where you are planted: Hemangioma or malignancy?

Vascular anomalies comprise a spectrum of disorders characterized by the abnormal development or growth of blood and lymphatic vessels. These growths have unique features and diverse behaviors, mandating a multidisciplinary approach in their evaluation, diagnosis, and management. Here we describe the case of a male toddler presenting with an abdominal mass, originally treated as a metastatic retroperitoneal tumor, but subsequently felt to represent a vascular anomaly.

Hypofractionated radiation in older women with breast cancer.

BACKGROUND: American Society of Radiation Oncology Choosing Wisely campaign recommends hypofractionated radiation and against routine use of intensity-modulated radiation therapy (IMRT) in early-stage estrogen receptor-positive breast cancer. We analyzed guideline recommendation adherence and financial implications in a modern Medicare cohort of women treated across the southeastern United States. METHODS: Our study population comprised Medicare patients over 65 years of age with breast cancer diagnosis from 12 cancer centers in the Southeast United States with stage 0-II breast treated with lumpectomy from 2012 to 2015. Hypofractionation was defined as 4 or fewer weeks of radiation treatments. Factors associated with utilization of hypofractionation and IMRT were identified using Poisson regression. Median costs during radiation treatments were compared for hypofractionation and IMRT. RESULTS: In older women (median age 71), 75% were treated with conventional fractionation, and 20% received IMRT. Hypofractionated women were more likely to have a positive estrogen(ER) or progestorone(PR) receptor status, lower comorbidity scores, and be treated at a high volume center (all P < 0.05). IMRT was utilized in 20% of patients and was more common in women treated with conventional fractionation (P < 0.001). Positive ER/PR status (P < 0.001) and utilization of hormonal blockade (P = 0.02) were associated with increased utilization of IMRT. CONCLUSION: In an older cohort of patients with early-stage breast cancer, a majority were treated with conventional fractionated radiation, while approximately 20% were treated with IMRT. Both of which were associated with increased cost relative to hypofractionation.

Acute Toxicity of Total Body Irradiation Using Volumetric Arc Therapy With a Focus on the Effect of Lung Dose Rate.

Purpose: To report adverse effects of high dose total body irradiation (TBI) delivered using a volumetric arc therapy (VMAT) technique and to assess pulmonary toxicity at dose rates of 40 and 100 monitor units per minute (MU/min). Methods and Materials: This retrospective study included patients >18 years old who received ≥8 Gy TBI using a VMAT technique. The TBI dose was prescribed to a planning target volume consisting of a 0.5 cm retraction of the body with the lungs subtracted. The objective function specified planning target volume coverage goals of D100% ≥ 90% and Dmax <130%. A lung dose control structure consisting of a 1 cm retraction of the lung volume was limited to Dmean <75%. Treatments were initially delivered with a dose rate of 40 MU/min for the thoracic isocenters and 100 MU/min for the other isocenters. Beginning in January 2021, a dose rate of 100 MU/min was used for all isocenters. All treatments were administered in 2 Gy fractions delivered twice daily. Acute toxicity was assessed for 30 days after TBI. Results: A total of 29 patients were included in this analysis who received TBI between January 2019 and October 2021. Prescription dose ranged from 8 to 12 Gy. Mean lung dose was 7.9 Gy (SD, 1.4 Gy) for patients treated at 40 MU/min and for patients treated at 100 MU/min 7.1 Gy (SD, 1.3 Gy). Mucositis was the most common grade 3 toxicity and occurred in 10 (34%) patients. Only 1 instance of pneumonitis was observed and occurred in a patient who received a mean lung dose of 10.1 Gy delivered at 40 MU/min. Conclusions: In this cohort of patients who received high dose TBI using a VMAT technique, the composite rate of acute toxicity was not unexpectedly high. We did not observe an increase in lung toxicity after increasing the dose rate of the thoracic isocenters from 40 MU/min to 100 MU/min.

Accelerated partial breast irradiation for early-stage breast cancer: controversies and current indications for use.

Radiation therapy options for early-stage breast cancer have evolved during the past 40 years. Several choices are currently available to certain patient subsets that allow radiation oncologists to individualize care. Multiple phase II and several phase III trials have been published that support the safety and efficacy of accelerated partial breast irradiation (APBI) as part of breast conservation in selected patients. In contrast, a recent large retrospective analysis of patients aged 67 or older who received brachytherapy for APBI has raised concerns about its effectiveness. As the radiation community awaits results from NSABP B-39/RTOG 0413, the largest randomized trial of whole breast radiation therapy (WBRT) versus APBI, to provide more conclusive data, many academic and private radiation oncology practices are utilizing APBI off-protocol to treat early-stage breast cancer patients. Because of this, the American Society for Radiation Oncology (ASTRO) published a consensus statement in 2009 to aid in proper patient selection (Table 1). Until more definitive data is garnered, we advocate strict adherence to these selection criteria to ensure optimal outcomes. Specifically, we caution against the use of APBI in lymph node-positive disease outside of a clinical trial. There is a paucity of comparative data to guide oncologists in selection of the best APBI delivery method. The current NSABP B-39/RTOG 0413 trial allows any of the three most common forms of delivery to be utilized (multicatheter interstitial brachytherapy, balloon intracavitary brachytherapy, and external beam 3D conformal therapy) and will be instrumental to compare outcome differences between these methods.

Molecular determinants of post-mastectomy breast cancer recurrence.

Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM, and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM, or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM, and 25 controls) identified significantly more NF1 mutations and mitogen-activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p < 0.0001 and p = 0.0070, respectively). Three patients had matched primary vs. LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) vs. controls (14%, p = 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.

A dosimetric comparison of electronic compensation, conventional intensity modulated radiotherapy, and tomotherapy in patients with early-stage carcinoma of the left breast.

PURPOSE: Intensity modulated radiation therapy (IMRT) has been shown to significantly reduce dose to normal tissue while maintaining coverage of the clinical target volume (CTV) in patients with intact breast cancer. We compared delivery of whole breast irradiation utilizing three techniques: electronic tissue compensation (ECOMP), inverse-planned dynamic multileaf collimation IMRT (DMLC), and tomotherapy (TOMO). PATIENTS AND METHODS: Ten patients with early stage, left-sided breast cancer were selected for planning. CTV was defined as breast encompassed in a standard tangent field minus the superficial 5 mm from the skin edge. Normal tissue contours included the heart, lungs, and contralateral breast. Plans included delivery of 45 Gy in 25 fractions and were normalized to ensure > or =95% coverage of the CTV. Isodose distributions and dose-volume histograms for CTV and normal tissue were compared between plans. The time it took to plan each patient excluding contouring, as well as number of monitor units (MUs) required to execute each plan were additionally tabulated. RESULTS: The TOMO plans resulted in significantly greater heterogeneity (CTV V(115)) versus ECOMP (p = 0.0029). The ECOMP plans resulted in significantly lower doses to heart, lung, and contralateral breast when compared with TOMO plans. The ECOMP plans were generated in the shortest time (12 min) and resulted in the lowest number of MUs when compared with DMLC (p = 0.002, p < 0.0001) and TOMO (p = 0.0015, p < 0.0001). CONCLUSIONS: The ECOMP plans produced superior dose distributions in both the CTV and normal tissue when compared with TOMO or DMLC plans. In addition, ECOMP plans resulted in the lowest number of MUs and labor cost.

Lower frequency of TLR9 variant associated with protection from breast cancer among African Americans.

INTRODUCTION: Toll-like receptor 9 (TLR9) is an innate immune system DNA-receptor that regulates tumor invasion and immunity in vitro. Low tumor TLR9 expression has been associated with poor survival in Caucasian patients with triple negative breast cancer (TNBC). African American (AA) patients with TNBC have worse prognosis than Caucasians but whether this is due to differences in tumor biology remains controversial. We studied the prognostic significance of tumor Toll like receptor-9 (TLR9) protein expression among African American (AA) triple negative breast cancer (TNBC) patients. Germline TLR9 variants in European Americans (EAs) and AAs were investigated, to determine their contribution to AA breast cancer risk. METHODS: TLR9 expression was studied with immunohistochemistry in archival tumors. Exome Variant Server and The Cancer Genome Atlas were used to determine the genetic variation in the general EA and AA populations, and AA breast cancer cases. Minor allele frequencies (MAFs) were compared between EAs (n = 4300), AAs (n = 2203), and/or AA breast cancer cases (n = 131). RESULTS: Thirty-two TLR9 variants had a statistically significant MAF difference between general EAs and AAs. Twenty-one of them affect a CpG site. Rs352140, a variant previously associated with protection from breast cancer, is more common in EAs than AAs (p = 2.20E-16). EAs had more synonymous alleles, while AAs had more rare coding alleles. Similar analyses comparing AA breast cancer cases with AA controls did not reveal any variant class differences; however, three previously unreported TLR9 variants were associated with late onset breast cancer. Although not statistically significant, rs352140 was observed less frequently in AA cases compared to controls. Tumor TLR9 protein expression was not associated with prognosis. CONCLUSIONS: Tumor TLR9 expression is not associated with prognosis in AA TNBC. Significant differences were detected in TLR9 variant MAFs between EAs and AAs. They may affect TLR9 expression and function. Rs352140, which may protect from breast cancer, is 1.6 X more common among EAs. These findings call for a detailed analysis of the contribution of TLR9 to breast cancer pathophysiology and health disparities.

Clinical experience with chronomodulated infusional 5-fluorouracil chemoradiotherapy for pancreatic adenocarcinoma.

PURPOSE: To evaluate retrospectively the efficacy and chronic toxicities of concurrent radiotherapy and chronomodulated infusion 5-fluorouracil (5-FU) in patients with pancreatic adenocarcinoma. METHODS AND MATERIALS: Twenty-eight patients with pancreatic adenocarcinoma were treated between January 1997 and May 2000 with 5-FU chronomodulated chemoradiotherapy. Chronomodulated delivery of chemotherapy was chosen on the basis of a lower toxicity profile in the treatment of GI malignancies. The median age was 64 years. Of the 28 patients, 12 were men and 16 were women. Eight patients had unresectable disease and 20 were treated after pancreatic resection. The median radiation dose was 50.4 Gy given in 28 fractions. The median field length and width was 10.6 cm and 10.9 cm, respectively. Concurrent chemotherapy with 5-FU was administered 5 d/wk, with a median total dose of 8.4 g/m2 (300 mg/m2/d). Chronomodulated 5-FU delivery consisted of a low basal infusion for 16 h followed by an 8-h escalating-deescalating infusion peaking at 10 pm. Survival and recurrence data were evaluated using Kaplan-Meier actuarial analysis. Toxicities were recorded using the Radiation Therapy Oncology Group grading system. RESULTS: The median follow-up for all patients was 26 months (range, 4-68 months). The median overall survival for the 20 patients treated postoperatively was 34 months, with a 3- and 5-year actuarial survival rate of 40% and 21%, respectively. If the 3 patients with carcinoma of the ampulla were removed from the data set, the mean overall survival in the resected patients was 34 months, with a 3-year and 5-year actuarial survival rate of 40% and 17%, respectively. The 8 unresectable patients had a median overall survival of 14 months, and none lived past 2 years. No patient experienced Grade 3 or 4 hematologic toxicity or weight loss. Five patients had nausea and dehydration requiring i.v. fluids; only one (4%) was hospitalized. Four patients required a dose reduction of 5-FU, one for nausea, one for a transient ischemic attack, one for an infection, and one because of myocardial infarction. Seven resected patients, four of whom had no evidence of disease, developed diabetes mellitus 1-2 years after radiotherapy. CONCLUSION: Chronomodulated 5-FU administration, based on the concept of chronotolerance, has relatively low acute toxicity. Our median survival rate was greater than that after most chemoradiotherapy programs that result in more acute toxicity. Additional study is warranted to evaluate chronomodulated radiosensitizing chemotherapy schedules in prospective trials and with attention to late effects after radiotherapy, including diabetes mellitus.

Patterns of Failure for Lymph Node-Positive Resected Pancreatic Adenocarcinoma After Adjuvant Radiotherapy or Gemcitabine-based Chemotherapy Alone.

PURPOSE: The purpose of this study was to investigate the effect of radiotherapy on local control and mordibity for patients with resected lymph node-positive pancreatic cancer as compared to gemcitabine-based chemotherapy alone. MATERIALS AND METHODS: Sixty-nine patients received adjuvant therapy for pancreatic adenocarcinoma with lymph node involvement after surgical resection and met the inclusion criteria for this analysis. Forty (58 %) patients received postoperative radiotherapy (PORT) to a median dose of 50.4 Gy with capecitabine or 5-fluorouracil concurrently in all but one case; 15 patients also received gemcitabine prior to PORT. Twenty-nine (42 %) patients received gemcitabine-based chemotherapy without PORT for a median of 6 cycles. RESULTS: The median overall survival for patients receiving PORT was 24.4 months compared to 25.6 months for patients not receiving PORT (p = 0.943). At 2 years, the rate of local control was 57 % for patients receiving PORT compared to 37 % for those who did not (p = 0.034). At 2 years, the rate of palliative local interventions was 16 % for patients receiving PORT compared to 18 % for patients who did not (p = 0.821). CONCLUSION: The use of PORT was associated with improved local control in the gemcitabine era for patients with resected, node-positive, pancreatic adenocarcinoma. The rates of overall survival and palliative interventions did not differ between the two groups.

Quantitative perfusion- and diffusion-weighted magnetic resonance imaging of gastrointestinal cancers treated with multikinase inhibitors: a pilot study.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) are often used to detect the early response of solid tumors to an effective therapy. The early changes in intratumoral physiological parameters measured by DCE-MRI/DWI have been evaluated as surrogate biomarkers allowing a tailored treatment for the individual patient. METHODS: Patients with newly diagnosed, biopsy-proven, treatment-naïve gastrointestinal stromal tumor (GIST) or hepatocellular carcinoma (HCC) were enrolled prospectively after institutional review board (IRB)-approved informed consent (5 patients per tumor type). Patients with GIST were treated with sunitinib over 6 weeks. DCE-MRI/DWI was applied before therapy (baseline imaging) and at 2 and 6 weeks after therapy initiation. Patients with HCC were treated with radiation during the first 2 weeks and then with sorafenib for the next 6 weeks. DCE-MRI/DWI was applied in all patients with HCC before and after radiation therapy and at the end of sorafenib therapy. Tumor volume, perfusion parameters (K (trans), the forward volume-transfer constant, and k ep, the reverse reflux-rate constant) and the apparent diffusion coefficient (ADC) were measured. RESULTS: During 2 weeks of sunitinib therapy, GIST volume, K (trans), and k ep decreased 32 ± 13, 45 ± 24, and 42 ± 15%, respectively, whereas ADC increased 76 ± 24%. After 6 weeks of sunitinib therapy, GIST volume, K (trans), and k ep decreased 56 ± 7, 70 ± 7, and 50 ± 12%, respectively, whereas ADC increased 85 ± 33%. After completion of radiation therapy, HCC volume, K (trans), and k ep decreased 34 ± 14, 35 ± 12, and 4 ± 21%, respectively, but ADC increased 21 ± 9%. During the entire 10-week therapeutic period, HCC volume, K (trans), and k ep decreased 65 ± 15, 40 ± 9, and 26 ± 2%, respectively, whereas ADC increased 28 ± 10%. CONCLUSION: DCE-MRI/DWI can measure the perfusion and diffusion changes in GISTs or HCCs treated with multikinase inhibitors.

Dosimetric analysis of imaging changes following pulmonary stereotactic body radiation therapy.

INTRODUCTION: The aim of this study was to determine whether late patterns of pulmonary fibrosis are related to specific radiation doses administered during thoracic stereotactic body radiation therapy (SBRT). METHODS: The records of all patients treated with SBRT for either pulmonary metastases or inoperable primary lung tumours at the University of Alabama at Birmingham from November 2005 to July 2008 were reviewed. Patients selected for analysis had diagnostic chest computed tomography (CT) scans acquired at least 180 days after completion of therapy. CT scans acquired at follow-up were co-registered with the original treatment planning CT scans for 12 eligible patients (17 lesions), and late-occurring pulmonary imaging abnormalities (IAs) were contoured. Dosimetric parameters analysed include D(80) , D(90) , V(18) and V(prescription dose) of the IA and V(14) and V(18) of the lung. RESULTS: Late pulmonary IAs were identified in 11 treated areas from nine patients. Late IAs could not be identified in six treated areas from three patients secondary to emphysema, tumour progression and severe atelectasis, respectively. The mean doses to 80% (D(80) ) and 90% (D(90) ) of the IAs were 18.4 and 14.5 Gy, respectively (ranges: 5.6-27.8 and 3.3-22.4 Gy). On average, 79.4% (range: 45.6-97.5%) of the IA received at least 18 Gy, while an average of 19.3% (range: 0.2-42.2%) received the prescription dose. On average, only 4.2% (range: 1.1-7.8%) of the lungs received 18 Gy. CONCLUSION: Imaging abnormalities consistent with pulmonary fibrosis are common after SBRT and are well approximated by the 18 Gy isodose distribution. The clinical ramification of these findings should be evaluated in future studies.

An imrt technique to increase therapeutic ratio of breast irradiation in patients with early-stage left breast cancer: limiting second malignancies.

The clinical application of intensity modulated radiotherapy (IMRT) for adjuvant treatment of breast cancer has been the subject of increasing study in recent years. IMRT results in improved target coverage, reduced dose inhomogeneity within the breast, and reduced dose to the heart, lungs, and contralateral breast. However, this has been at the cost of larger volumes of low-dose radiation to these structures, thus increasing the theoretic risk for second malignancies. Our goal was to develop an IMRT beam arrangement that did not result in additional low-dose spill to organs at risk while maintaining equal or better target coverage. Five patients with early-stage left-sided breast cancer, who underwent breast conservation surgery and adjuvant radiation therapy, were chosen for this comparative study. The conventional radiation treatment (CRT) plan was comprised of standard wedged tangential fields. An IMRT plan consisting of 6 tangential beams (3 medial and 3 lateral) was generated by using the gantry, collimator, and table angles of the standard plan used for the CRT plan, and moving the table +10 degrees and -10 degrees on each side. The prescription dose for both CRT and IMRT plans was 45 Gy, 1.8 Gy/fraction, prescribed to the isocenter, which was placed near the center of the breast. IMRT plans provided significantly better coverage of the left breast than the CRT plans (p = 0.03). Although the dose heterogeneity was greater with the IMRT plans, the difference was not significant (p = 0.68). The mean volumes of the heart, lung, and right breast were lower in patients planned with IMRT at all dose levels from 5% to 100% dose (5% increments). This difference was significant for volumes receiving 2.25 Gy for the heart (p = 0.003), and volumes receiving 2.25, 4.5, 6.75, 33.75, 36, 38.25, and 42.75 Gy for the lung (p = 0.014, 0.04, 0.044, 0.05, 0.049, 0.045, and 0.05, respectively). Surprisingly, breast IMRT resulted in significantly lower right breast volumes irradiated at all dose levels compared to CRT. A 6-tangential-field IMRT technique achieved significantly better left breast coverage while maintaining lower doses to risk organs at all dose levels and therefore reduced the potential for induction of a second malignancy.

Five-year results of a phase II trial of hyperfractionated radiotherapy and concurrent daily cisplatin chemotherapy for stage III non-small-cell lung cancer.

The purpose of this study was to evaluate the 5-year results for a phase II trial of hyperfractionated radiotherapy (RT) and concurrent daily cisplatin chemotherapy. Between August 1994 and December 1999, 63 patients with stage IIIA and stage IIIB non-small-cell lung cancer were treated with RT to a dose of 69.6 Gy at 1.2 Gy twice daily with daily cisplatin at 6 mg/m. Thirty-seven patients elected to receive consolidation carboplatin and paclitaxel chemotherapy. Recurrence and survival outcomes were evaluated by Kaplan-Meier analysis. Acute and late side effects were scored by the Radiation Therapy Oncology Group (RTOG) grading system. Radiographic complete or partial tumor response was achieved in 34 of 63 (54%) of cases. Median absolute survival was 20.1 months. Median time to local recurrence and distant metastases were 10.6 and 8.6 months, respectively. Overall survival rates were 57%, 35%, and 23% at 1, 3, and 5 years, respectively. Survival was significantly greater for patients receiving consolidation chemotherapy (50% versus 20% at 3 years). Only 5 patients (7%) experienced Grade 3 or 4 esophagitis. There were 16 cases of Grade 1 or 2 pneumonitis; steroid therapy resolved symptoms in 9 patients. This regimen of hyperfractionated RT and chemotherapy achieved significant response, and 5-year survival rates with acceptable toxicity.