Rib Metastasis Research Articles

Advanced medullary thyroid carcinoma uncovered by persistently elevated procalcitonin in a patient with COVID-19.

We report the case of an 88-year-old man hospitalized for COVID-19 with persistently very high procalcitonin (proCt) levels despite infection resolution. Since proCt is an adjunct tumor marker in the diagnosis of medullary thyroid carcinoma (MTC), serum calcitonin (Ct) was also measured showing very high levels. Computed tomography (CT) scan showed the presence of a thyroid mass and neck ultrasound revealed a solid isoechoic, inhomogeneous, 50 mm nodule in the right thyroid lobe, extended into the mediastinum. Fine needle aspiration (FNA) of the thyroid nodule confirmed the diagnosis of MTC. An 18F-fluorodopa positron emission tomography/computed tomography (PET/CT) scan revealed the presence of distant metastases in ribs, vertebrae, in the right iliac wing and the liver. Since surgery was not feasible, the patient was started on cabozantinib 40 mg/dL. After 16 months the patient is still on cabozantinib at the same dose, he reports complete autonomy in daily life activities, and serum Ct is still elevated; however, the imaging evaluation does not show signs of disease progression. High procalcitonin serum values despite the absence of infection are suggestive of MTC. Advanced MTC with multiple metastases can have an indolent course and can go unrecognized for years. Cabozantinib is a valuable option for the treatment of advanced MTC.

Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Predictors of pathologic fracture and local recurrence following stereotactic body radiation therapy to 505 non-spine bone metastases

PurposeStereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database. MethodsPatients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF. ResultsA total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy10 decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR. ConclusionSBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.

A case in which ultrasonography was useful in differentiating between rib fracture due to compression after biopsy and rib metastasis of breast cancer.

A case in which ultrasonography was useful in differentiating between rib fracture due to compression after biopsy and rib metastasis of breast cancer.

Stereotactic Body Radiation Therapy for Non-Spine Bone Metastases: Local Control and Fracture Risk

<h3>Purpose/Objective(s)</h3> Stereotactic Body Radiation Therapy (SBRT) is increasingly being utilized to treat non-spine bone metastases (NSBM) with both palliative and radical intent. There remains limited data on the long-term outcomes and toxicities and, therefore, we report mature results from our institutional database. <h3>Materials/Methods</h3> Patients with NSBM who were treated with SBRT were identified from 2011 to 2021. The primary endpoint was radiographic local failure (LF). Secondary endpoints included rate of in-field pathologic fracture (PF), overall survival (OS), and late (>3 months post-SBRT) grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). Competing risks analysis was used to assess rates of LF and PF. OS was estimated using the Kaplan-Meier method. Univariable regression (UVR) and multivariable regression (MVR) were performed to investigate predictive factors for LF and PF. <h3>Results</h3> A total of 373 patients with 505 NSBM were included in this study. Primary indications for SBRT included oligometastatic disease (52.6%), pain relief (23.8%), and oligoprogression (19.7%). Median follow-up was 26.5 months (range: 3.0-128.3 months). The most common primary histologies included prostate (33.7%), RCC (20.7%), breast (16.9%), and lung (14.8%). The two most common NSBM sites were pelvic (42.3%) and rib (30.5%). Of all NSBM, 217 (42.7%) were lytic and 230 (45.3%) were symptomatic. The most common dose prescriptions were 35 Gy in 5 fractions (33.3%) and 24 Gy in 2 fractions (25.2%). The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. There were 3 instances of late grade ≥3 toxicity: 1 grade 3 osteonecrosis, 1 grade 3 peripheral neuropathy, and 1 grade 5 bowel fistula. Median OS was 53.9 months (95% confidence interval: 45.3-63.2 months). Lytic NSBM (HR=2.20; p<0.01), symptomatic NSBM (HR=2.15; p<0.01), and those with a larger PTV (HR=1.01; p=0.04) were at higher risk of LF on MVR. Lytic lesions (HR=3.43; p<0.01), mixed (lytic/sclerotic) lesions (HR=2.70; p=0.04), and rib metastases (HR=2.68; p<0.01) were at a higher risk of PF on MVR. <h3>Conclusion</h3> SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of fracture. We identify predictors of both LF and PF that can serve to inform practice.

Intensity Modulation in Electron FLASH Radiotherapy

<h3>Purpose/Objective(s)</h3> Combining methods of conformal dose delivery with ultra-high dose rate (UHDR) beams is advantageous for realizing the benefits of the FLASH effect in clinical treatments. We hypothesize that deployment of intensity modulation in passive electron FLASH radiotherapy through treatment plan optimization is feasible. <h3>Materials/Methods</h3> A beam model of an electron FLASH irradiator (delivering ∼300Gy/s at the isocenter) in the decimal ElectronRT treatment planning system (TPS) was validated with film measured lateral and percent-depth-dose (PDD) profiles. Plans were developed comparing collimated open fields and intensity modulated electron beams achieved with cylindrical passive metal compensators that vary in spacing and size. Homogeneity and conformity were quantified for plans developed in a water phantom and anonymized patient cases considering constraints in prescribed dose to the target volume and minimizing dose to organs-at-risk (OAR). <h3>Results</h3> The film measured profiles and TPS beam model agreed on average to within 1% and 2% for lateral profile and PDD, respectively. For a large 15 × 15 cm² field in a water phantom the intensity modulation improved the beam flatness (∼30% to <5%) and penumbra (35 mm to 15mm) at 3 cm depth while retaining UHDR in the treatment field with a 38% reduction in central axis output while still retaining the UHDR conditions (∼180Gy/sec). The PDD exhibited <2% difference along the central axis and minimal changes to symmetry, shift, and practical range. In the rib metastasis case, the unmodulated and modulated plans treat the tumor volume with a homogeneity index (HI), improvement by 0.2. In the facial orbital plan, the conformity index improved by 8% with an improvement in HI by 0.05 and comparable dose to OARs. <h3>Conclusion</h3> Intensity modulation of electrons FLASH is achievable and improves homogeneity of prescribed dose with proper treatment constraints while reducing hot spots for clinical plans. Depending on the treatment case intensity modulation can also generate superior dose distributions while retaining the UHDR conditions to best exploit the FLASH effect. Future study will focus on demonstrating dosimetric benefits quantified by tumor control probability and normal tissue complication probability models in a larger number of relevant cases.

Risk factors for rib metastases of lung cancer patients with high-uptake rib foci on 99Tcm-MDP SPECT/CT.

99Tcm-MDP SPECT/CT is widely used to diagnose early bone metastasis. Ribs are high-risk bone metastasis sites, while few study is related to ribs. The study is to investigate the risk factors of rib metastases in lung cancer patients. We retrospectively analyzed the patients' clinical characteristics and SPECT/CT imaging features. The patients were divided into a rib metastasis group (108 cases) and a non-rib metastasis group (103 cases). In 211 patients, rib metastases were closely related to tumor markers, T stage, N stage, clinical staging, lymph node (LN) involvement, number of rib foci, localization on rib and foci type (P<0.05). In 93 patients with pure rib foci, rib metastases were affected by clinical staging, LN involvement, localization on the rib and primary lung cancer localization (P<0.001, 0.038,<0.001, 0.034, respectively). In 100 patients with a solitary rib focus, rib metastases were associated with clinical staging, localization on the rib, and LN involvement (P<0.001, 0.001, and 0.014, respectively). In all 633 rib foci, localization on the rib was an effective risk factor for rib metastases (P<0.001). Patients with increased tumor markers, stage IV lung adenocarcinoma and multiple rib foci located ipsilaterally with the primary lung tumor, or rib foci accompanied other bone foci are more likely to develop rib metastasis. Patients with pure rib foci or a solitary rib focus, especially in the anterior rib with negative LN involvement, have a low probability of rib metastasis.

Surgical treatment of patients with chest wall metastases

To evaluate postoperative outcomes in patients with chest wall metastases. We analyzed 40 patients who underwent surgery for chest wall metastatic lesions. Fourteen (35%) patients had sternal lesion, 26 (65%) ones - rib metastases. We used implants for chest wall defect closure in 15 (37.5%) patients. Chest wall repair with autologous tissues was performed in 19 (47.5%) patients. Median survival was 17 months. Most patients (n=30, 75%) showed improvement in the quality of life according to Karnofsky and EGOG scale after surgery. Continued tumor growth occurred in 4 (10%) patients within 8-16 months after surgery. There were 2 patients who suffered from tumor recurrence accompanied by other metastatic foci (progression). Complications were diagnosed in 5 (12.5%) patients. Tactical errors were identified in 4 (10%) patients and they were associated with progression of cancer in the form of new metastatic foci within 6 months after surgery. Active surgical approach for bone metastases in patients with favorable cancer-related prognosis can improve quality of life and survival at least in case of solitary lesions. New program for treatment strategy selection based on prognosis of life expectancy and algorithms of surgical treatment will reduce the risk of erroneous management and increase its effectiveness.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features and the risk of malignancy in thyroid cytology: Data from Singapore

The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on the risk of malignancy (ROM) in fine-needle aspiration cytology (FNAC) per The Bethesda System for Reporting Thyroid Cytopathology has not been well reported in Singapore. We retrospectively identified 821 thyroid nodules with preoperative FNAC from 788 patients out of 1,279 consecutive thyroidectomies performed between January 2010 and August 2016 in a tertiary general hospital in Singapore. Possible cases of NIFTP were reviewed for reclassification and the impact of NIFTP on ROM was analysed. The incidence of NIFTP was 1.2% (10 out of 821). If NIFTP is considered benign, ROM in Bethesda I through VI were 8.6%, 3.5%, 26.3%, 20.0%, 87.7%, 97.0% versus 8.6%, 4.2%, 28.1%, 26.7%, 89.2% and 100% if NIFTP is considered malignant. Eight patients with NIFTP had follow-up of 15 to 110 months. One had possible rib metastasis as evidenced by I131 uptake but remained free of structural or biochemical disease during a follow-up period of 110 months. None had lymph node metastasis at presentation, nor locoregional or distant recurrence. Classifying NIFTP as benign decreased ROM in Bethesda II through VI, but the benignity of NIFTP requires more prospective studies to ascertain. The impact of NIFTP on ROM in our institution also appears to be lower than that reported in the Western studies.

A Possible Abscopal Effect Of Radioimmunotherapy in a Patient With Advanced Oligometastatic Adenocarcinoma of the Lung

"Two randomized phase III studies provided cumulated long-term results, comparing second line treatment with Nivolumab versus Docetaxel in advanced non-small cell lung cancer (NSCLC). With the advent of modern immunotherapy (IO), the potential for even more immune activation by radiation therapy, inducing tumor specific immunity led to a novel role for radiotherapy in systemic disease. This case proposes to evaluate the benefit of second line immunotherapy with Nivolumab, a PD-1 checkpoint inhibitor, and hypofractionated radiotherapy, in a patient with advanced oligometastatic adenocarcinoma of the lung, with progressive disease after first line chemotherapy, and the analysis of a possible abscopal effect. A 50-year-old male, heavy smoker with a 30 years-pack index, presented with a history of left posterior thoracic pain. MRI identified an osteolytic lesion on the 10th rib and CT scan showed an additional 25 mm nodule in the left upper lobe (LUL) and a 7 mm nodule in the left lower lobe (LLL). Atypical resections of the nodules and resection of the osteolytic lesion of the rib were performed. The pathological examination revealed a G2 adenocarcinoma of the lung (ALK and EGFR negative) pT4Nx pM1 with metastases in the rib and pleura, with unspecified margins. Chemotherapy was administered, with complete response on imaging after 6 cycles of Gemcitabine/Carboplatin, and hematologic toxicity. After 7 ½ months a regional and distant progression of the disease with metastases on the 7th and 10th rib was revealed on PET-CT. Palliative hypofractionated radiotherapy was administered to a dose of 20 Gy/ 5 fr to the painful 7th rib metastasis and the patient started second line treatment with Nivolumab, 240 mg iv q2wks. Three years later, at his last follow-up in Nov 2021, the patient maintains a (PET)-CT complete response, with no adverse events. A possible abscopal effect may be suspected in this case."

Treatment Planning System for Clinical Translation of Electron FLASH Radiotherapy

Electron ultrahigh dose rate FLASH radiotherapy (UHDR/eFLASH-RT) is currently being extensively tested and modeled, and was studied in several rodent and large animal experiments and one clinical cancer patient. These studies suggest prospective dosimetry assessments are necessary to ensure safe delivery and widespread clinical translation of eFLASH-RT would clearly benefit from prior dose prediction and a treatment planning process that accounts for anatomical heterogeneity and complex geometries. In this study, a GAMOS Monte Carlo beam model was developed and implemented in a clinical treatment planning system for a modified UHDR electron LINAC to demonstrate eFLASH-RT planning of patients.The gantry head was modelled without scattering foils or targets, representative of the LINAC modifications. Centered at the nominal energy of 10 MeV, the energy spectrum (σE) was varied to match the central axis percent depth dose (PDD) profiles of an open field measured with radiographic film. The beam's emittance cone angle (θcone) was determined by matching calculated and film measured lateral profiles, at several depths. The beam model and its configuration in the treatment planning system were validated with film measured lateral profiles and PDD's of the open field and nominal fields for clinical applicators. A GAMOS forward dose calculation was conducted for a mouse whole brain treatment and an eFLASH-RT plan was compared to a conventional electron plan for a human patient with a rib metastasis.Our eFLASH beam model agrees best with measurements at σE = 0.5MeV and θcone = 3.9o ± 0.2o. The model and its treatment planning system configuration were validated to clinically acceptable accuracy (the absolute average error was within 1.5% for in water lateral, 3% for in air lateral, and 2% for PDD's). The forward dose calculation showed dose was delivered to the entire mouse brain with adequate conformality (90% of the tumor volume receiving 90% of the prescribed dose). The comparison plans for the patient undergoing treatment for a rib metastasis demonstrated the capability to achieve an acceptable eFLASH-RT plan with routine accessories (90% of the tumor receiving 95% and 90% of the prescribed dose for eFLASH and conventional, respectively) in relatively complex geometry (right posterior oblique treatment with patient specific applicator cutout).To the best of our knowledge, this study presents the first functional beam model commissioned in a clinical TPS for eFLASH-RT, enabling treatment planning and evaluation with minimal deviation from conventional radiotherapy workflow. By producing plans with the quality comparable to conventional plans, specifically for human patients involving complex geometries and tissue heterogeneity, the clinical translation of eFLASH-RT can be expedited. The open-source methods (described in https://github.com/mr3536/eFLASHBeamModeltoTPS) can model other eFLASH irradiators with different beam characteristics.

A case of chest wall resection and reconstruction for solitary rib metastasis of pancreatic cancer

A case of chest wall resection and reconstruction for solitary rib metastasis of pancreatic cancer

Pneumonitis following Pembrolizumab and radiation therapy in a patient with lung cancer and rib metastasis

Pneumonitis following Pembrolizumab and radiation therapy in a patient with lung cancer and rib metastasis

Risk Factors of Rib Metastases in Nasopharyngeal Carcinoma Patients with Rib 99mTc-MDP Foci on Whole-body Bone Scans

目的分析鼻咽癌全身骨扫描肋骨99mTc-MDP高摄取灶与肋骨转移率及各临床因素之间的关系，筛选肋骨高摄取灶的骨转移危险因素。 方法对312例全身骨扫描出现肋骨99mTc-MDP高摄取灶的鼻咽癌患者进行回顾性分析。采用卡方检验和Logistic回归分析临床因素与肋骨转移的关系。 结果 312例鼻咽癌患者中，肋骨高摄取灶骨转移率在T分期、颅底骨侵犯、其他骨转移、摄取灶数量、双侧肋骨分布范围、是否合并肺外摄取灶上均存在显著差异（均P 结论鼻咽癌肋骨99mTc-MDP高摄取灶的骨转移危险因素包括颅底骨侵犯、其他骨转移、双侧肋骨分布范围、是否合并肺外摄取灶、摄取水平、前后位置。单侧肋骨的单纯性高摄取灶，以随访为主；而双侧肋骨的多发高摄取灶或单发肋骨高摄取灶合并其他骨摄取灶时，需进一步断层影像检查以排除骨转移。

The clinical efficacy of ultrasound-guided percutaneous microwave ablation for rib metastases with severe intractable pain: a preliminary clinical study.

Purpose: To retrospectively evaluate the clinical efficacy of ultrasound-guided percutaneous microwave ablation (US-PMWA) for patients with rib metastases that caused severe intractable pain.Materials and methods: From Jan 2016 to Apr 2018, 9 rib metastases from 7 solid tumor patients were treated with US-PMWA. The visual analogue scale (VAS), daily opiate intake doses, local tumor control and complications were recorded and analyzed.Results: The follow-up period ranged from 6 to 33 months (median: 16 months). The procedures were successfully performed in all of the patients by one ablation. The ablation power ranged from 30 to 60 W, and the ablation time was 610.0±317.5 s. The mean preablation VAS pain score was 8.1±0.7, whereas the mean VAS pain score at 72 h postablation was 3.3±0.5 (P<0.001). All of the patients needed to apply oral and/or intravenous injection opiates to relieve severe intractable pain before ablation, with daily opiate intake doses of 61.4±30.8 mg. After ablation, five patients did not need to apply any opiate treatments 72 h after ablation, and only two patients needed oral opiates (daily opiate intake doses: 30 mg and 20 mg). Recurrence was detected in three lesions at 6, 11 and 9 months after ablation, with the maximum diameter observed being more than 4 cm. All of the patients were alive during the follow-up period. No minor or major complications occurred.Conclusion: US-PMWA appears to be feasible, convenient, safe and effective in the palliative management of refractory pain caused by rib metastases. This treatment can improve the quality of life of patients and may also achieve promising local control of tumors.

Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: A retrospective analysis

ObjectivesPneumonitis related to the use of anti-programmed death 1 (PD-1) antibodies is a common immune-related adverse event that can be life-threatening. However, the relationship between pulmonary fibrosis/emphysema and the incidence of anti-PD-1-related pneumonitis is unclear. Materials and methodsWe retrospectively reviewed data from 123 patients who were diagnosed with non-small-cell lung cancer and treated with anti-PD-1 antibodies (nivolumab or pembrolizumab) at the Aichi Cancer Center Hospital, Japan, between December 17, 2015, and November 30, 2017. Patients who previously received thoracic radiotherapy to the primary lesion, mediastinum, spinal, or rib metastases were excluded from the analysis. Fibrosis score (0–5) and emphysema score (0–4) on baseline chest computed tomography (CT) were determined by two diagnostic radiologists. ResultsEighteen patients (14.6%) experienced anti-PD-1-related pneumonitis, of which four (3.3%) were grade ≥3. The median onset time of pneumonitis after starting anti-PD-1 therapy was 60 days (range, 6–634 days). According to the analysis of fibrosis score, pneumonitis occurred in 13 (35.1%) of the 37 patients with a fibrosis score ≥1 and in 5 (5.8%) of 86 patients with a fibrosis score of 0. Univariate and multivariate logistic regression analysis revealed that fibrosis score ≥1 was the only risk factor for anti-PD-1-related pneumonitis (p = 0.0008). ConclusionOur results indicate that pre-existing pulmonary fibrosis significantly increases the risk of anti-PD-1-related pneumonitis. Further studies are needed to identify predictive factors of anti-PD-1-related pneumonitis in patients with fibrotic changes on CT findings.

Giant abdominal sarcoma that caused aortic rupture at the twelfth thoracic level

There are no previous reports of intraabdominal sarcoma with metastasis to the thoraco-abdominal aorta causing rupture. Here we present the case of a previously healthy 50-year old male who presented to our institution with sudden, sharp back pain. Chest and abdominal computed tomography revealed aortic rupture at the twelfth thoracic level as well as a giant mass in the left upper abdomen. We performed thoracic endovascular aortic aneurysm repair. Histopathology of a biopsy taken from a rib metastasis was thought to be either differentiated liposarcoma or malignant fibrous histocytoma. The patient is currently undergoing chemotherapy.<Learning objective: Abdominal aortic rupture due to direct infiltration of sarcoma has been reported. However, there is no report that the metastasis of sarcoma caused the aortic rupture. Our report indicates the possibility that giant intraperitoneal sarcoma can cause aortic rupture due to para-aortic lymph node metastasis.>

Abstract 2076: Targeting the FGFR pathway in androgen receptor negative castration resistant prostate cancer

Abstract Metastatic castration-resistant prostate cancer (CRPC) has a poor prognosis and remains a significant therapeutic challenge. The continued importance of androgen receptor (AR) signaling as a growth and survival pathway in most advanced prostate cancer (PC) has prompted the development of therapeutics directed toward further suppressing AR ligands or the AR itself. However, total androgen blockade can give rise to AR-negative PC and currently there are no effective therapies for AR-negative PC. We have developed two novel patient-derived xenograft (PDX) models from a liver metastasis and a rib metastasis of a patient with CRPC: LuCaP 173.1 (Neuroendocrine; NE) and LuCaP 173.2 (Double negative: DN (AR-negative and NE-negative)). Using RNA-Seq we observed that both of these lines express high levels of fibroblast growth factors (FGF’s) and downstream effectors. We hypothesized that FGF signaling promotes survival and proliferation of NEPC and DNPC. To determine if blocking the FGFR survival pathway can attenuate the growth of NEPC/DNPC tumors, to characterize the molecular response and resistance to FGF signaling inhibition, and to support further evaluation in the clinic, we treated both PDX models with the FGFR inhibitor CH5183284. CH5183284 significantly reduced LuCaP 173.2 tumor volume (TV) (p&amp;lt;0.0001). The reduction in TV in CH5183284-treated animals bearing LuCaP 173.1 tumors was not as significant. To address this difference, we analyzed FGFR1 expression at the transcript and protein levels. Analysis of the FGFRs in the LuCaP 173.1 PDX model revealed a loss of FGFR1 expression. FGFR2 and FGFR3 transcripts were expressed at similar levels in both PDXs. The loss of FGFR1 expression may explain the low efficacy of CH5183284 in the LuCaP 173.1 PDX model. We are currently assessing the molecular pathways impacted by FGFR inhibition and mechanisms of resistance to treatment in these studies. We have demonstrated that FGFR inhibition attenuated tumor growth in FGFhigh AR-negative PC. We intend to target the FGFR survival pathway in additional NE and DNPC PDX models to investigate tumor heterogeneity in response to therapy and identify mechanisms of resistance. These studies will provide translational evidence that FGFR inhibitors could represent a new therapy for CRPC patients with AR-negative PC. Citation Format: Colm Morrissey, Eva Corey, Lisha Brown, Ilsa Coleman, Holly Nguyen, Michael Schweizer, Peter Nelson. Targeting the FGFR pathway in androgen receptor negative castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2076. doi:10.1158/1538-7445.AM2017-2076

Melanoma patient response to nivolumab treatment for metastatic lung lesions: Multi-OMICS analysis in Project HOPE.

A 70-year-old woman was diagnosed with a malignant melanoma of the occipital skin which was resected; however, multiple lung metastases were detected. Nivolumab therapy was initiated and partial response was obtained. However, the patient was diagnosed with grade 2 interstitial pneumonitis. Prednisolone administration was initiated and the interstitial pneumonitis shadow disappeared. However, then a right rib metastasis was noticed and given radiation therapy. After progressive disease was obtained, the metastatic lesion was resected, and no relapse occurred until skeletal muscle metastasis was found. According to whole-exome sequencing and gene expression profiling, the rib and skeletal muscle metastatic lesions showed an upregulated expression of programmed death-ligand 1 mRNA and a high single-nucleotide variant (SNV) number. The current melanoma case is representative of a patient who responded to nivolumab therapy, and showed typical immunological markers for responders such as high PD-L1 expression and high SNV.

Application of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia for controlling refractory pain induced by rib metastasis of lung cancer (a STROBE-compliant article).

This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy.This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0.5 to 1 mL of adriamycin (0.5%). The conditions of pain and complications were observed before management and 3 days, 1 month, and 3 months after management, respectively.Numerical rating scale (NRS) scores and dosage of morphine were all significantly decreased after management as compared with those before management (all P < 0.01). Although the number of patients with chest wall numbness was significantly increased after management as compared with that before management (all P < 0.01), the degree of chest wall numbness was tolerable. There were no statistical differences between before and after management in nausea and vomiting, and constipation.CT-guided radiofrequency thermocoagulation combined with adriamycin injection in DRG can effectively control lung cancer rib metastasis-related pain which has no response to conventional therapy. This combinatory treatment regimen is featured by better therapeutic effects and a few complications, so it is worthy of being recommended in clinical application.