Bony Metastases Research Articles

Implementation of a rapid access multidisciplinary bone metastases clinic to improve access to care at a large cancer center.

79 Background: MD Anderson Cancer Center is a large cancer center with 44,000 new patients per year. Radiation therapy (RT) is an effective treatment for bone metastases that can reduce pain medication use and improve quality of life. Our goal was to assess the effect of implementing a rapid access multidisciplinary clinic for bone metastases (RABC). Methods: RABC was instituted to schedule patients for radiation oncology and orthopedic surgery consult within 48 hours of referral. Same day simulation and treatment times were held for these patients for one 8Gy fraction. Thirty sequential patients treated with one fraction to bony sites in the outpatient setting prior to implementation of the clinic were chosen as a comparison group. Time from consult order to consult visit (OTV) and from consult visit to treatment completion (CTT) were recorded, in addition to frequency of multidisciplinary care (MDC; orthopedic surgery and radiation oncology). Overall Time (OT) was calculated from referral to treatment completion. T-test and chi-square test were used for analyses. Results: Between April 2018 and July 2018, 72 patients were referred to RABC. 23 patients were seen in consultation and received RT. Sites treated were pelvis (N = 10), spine (N = 6), lower extremity (N = 4) and upper extremity (N = 3). Patients had one site (N = 20), two sites (N = 2) or three sites treated (N = 1). Histologies included breast (N = 5), thoracic (N = 7), gastrointestinal (N = 6), genitourinary (N = 2) and head/neck (N = 2). OTV was shorter for RABC patients (mean 3.3 [+/-5.7] vs. 9.5 days [12.4]; p = 0.02). CTT was also significantly shorter for RABC patients (mean 5.4 hours [+/-1.8] vs. 6.5 days [+/-6.5]; p < .0001). OT was also shorter (3.5 days [+/-5.6] vs. 16.4 days [+/-14.8]; p < .0001). RABC clinic patients were more likely to receive MDC (100% vs 28%; p < .0001). Conclusions: The rapid access bone metastases clinic significantly decreased overall time from consult to completion of treatment and also decreased time to access radiotherapy. Patients were also more likely to receive multidisciplinary evaluation. The RABC approach is a promising model to improve palliation for patients with painful bony metastases.

Thoracic aorta aneurysm- a rare cause of chronic backache with mediastinal shadow: case report

<p class="abstract">Thoracic aortic aneurysms (TAA) are rarely symptomatic. A 55 year old male presents with longstanding chronic backache. CXR showed left hilar shadow with collapse of left lung. Considering the CXR findings and with the patient being chronic smoker a strong possibility of carcinoma lung with bony metastasis was kept and further CECT chest was done. The CECT chest was suggestive of a thoracic aorta aneurysm with thrombosis compressing left principal bronchus and its lower lobar branch resulting in distal area of collapse and consolidation of left lower lobe. These findings were further confirmed on CT angiography. The patient was thus diagnosed as a case of descending thoracic aorta aneurysm probably of atherosclerotic etiology with thrombosis. Patient was started on beta blockers and ACE inhibitors along with supportive and symptomatic treatment and was further transferred to the department of CTVS for surgical intervention. Thus, this case report here signifies that possibility of thoracic aorta aneurysm should always be considered in a patient with chronic backache specially in presence of mediastinal shadow on CXR.</p>

Metastatic Hepatocellular Carcinoma Presenting as Extensive Bone Metastasis

Hepatocellular carcinoma(HCC) is a primary malignancy of the liver and occurs mainly in patients with underlying chronic liver disease or cirrhosis. It is considered the third leading cause of cancer death worldwide. Here, we present a rare case of HCC with diffuse bone metastasis. 57 y.o. male with past history of Chronic Hepatits B & C presented with diffuse body aches associated with jaundice. Exam did not show any ascites or stigmata of cirrhosis. Relevant labs included: AST 62 ALT 53 Alk Phos 231 T Bili 1.6 INR 1.0 Alb 3.5 CEA 1.46 AFP 5.1. Multiple hepatic lesions seen on imaging were initially concerning for metastatic disease. Bone imaging revealed diffuse lytic lesions, with the largest in the right sacrum. No clear primary malignancy was identified, so patient underwent EGD and colonoscopy, which were negative. A sacral bone biopsy was performed, revealing atypical cells with abundant cytoplasm and abnormal nuclei (Image 1); further reticulin (Image 2), arginase, and heppar (Image 3) staining confirmed malignant hepatic cells. Patient was diagnosed with primary HCC with bone metastasis, Child Pugh score A. Due to the advanced nature of presentation, patient opted for Hospice care. HCC is often seen with early metastasis to lungs, abdominal lymph nodes, central nervous system, and bones—further decreasing median survival. Current treatment options for extra-hepatic HCC generalized to all metastatic types recommends palliative chemotherapy if Child Pugh A/B, and advises only symptomatic treatment if Child Pugh C. HCC with bony metastasis is rare, and is associated with even higher mortality rates and median survival of 3 months without treatment. Chemotherapy with Sorafenib can prolong median survival by on average 2 months, but with significant effect on standard of life due to side effects. Radiation therapy has shown improvement in pain without improved mortality. Other symptomatic treatment includes palliative stents, vitamin D, calcium, and pain control. In deciding care for HCC with bony metastasis, the net clinical benefit of each treatment must be considered by weighing the improvement in survival time versus quality of life. Interventions should focus on maximizing the individual's self-established quality-adjusted life years. Therefore, careful discussion is needed in each case to determine the best option for each patient.2311_A Figure 1. Bone biopsy showing atypical cells with abundant cytoplasm and enlarged round to ovoid nuclei. Together with staining patterns is consistent with HCC.2311_B Figure 2. Reticulin immunohistochemical stain suggestive of hepatic origin.2311_C Figure 3. Heppar immunohistochemical stain positive consistent with cells of hepatic origin.

What Is the Role of Upper Endoscopy in Patients With Gastric Pneumatosis?

Gastric pneumatosis is a rare finding. It can be seen with both gastric emphysema and emphysematous gastritis. Both may have similar presentations and differentiating between the two conditions is difficult radiographically. However, making the distinction between them is crucial; as GE has a benign clinical course while EG is more maleficent, and carries significant mortality. Early endoscopy may help differentiate between the two processes. We present a series of two immunocompromised patients that presented with radiographic findings consistent with gastric pneumatosis. A 52 y.o male with history of HIV, diabetes, and dialysis dependent end-stage renal disease presented with a 3-day history of epigastric fullness, vomiting, and chills. He was febrile at 101.6F and his abdominal exam revealed mild distension, active bowel sounds with no appreciable tenderness. CT abdomen revealed a distended stomach with air within the gastric wall as well as the presence of portal venous gas. Endoscopy was performed on the 2nd day of hospitalization and showed erythematous gastric mucosa in the body and antrum. He improved with conservative measures including antibiotics and was eventually discharged. The second case was a 58 y.o female with history of stage 4 squamous cell lung carcinoma with bony metastases, ESRD on dialysis, systolic heart failure, and diabetes who presented with left hip pain and found to have left proximal femur erosion with effusion and was admitted for hemiarthroplasty. On POD #1 she became unstable and was transferred to the MICU. A CT abdomen revealed portal venous gas with pneumatosis of the stomach and adjacent duodenum. Endoscopy performed the same night revealed a diffusely ulcerated, edematous hemorrhagic gastric mucosa sparing the pre-pyloric region. The patient was a poor surgical candidate and was subsequently managed medically. Despite resuscitative efforts the patient experienced cardiac arrest and expired. Treatment for GE is supportive as this condition tends to be self limiting. Management of EG is more active including correction of acid-base and electrolyte abnormalities, fluid resuscitation and IV antibiotics. Gastrectomy may be necessary in EG if medical management fails. As both conditions can present similarly differentiating between the two is pivotal. We found early endoscopy helped guide our management. We recommend consideration of endoscopy as part of the evaluation of patients presenting with gastric pneumatosis.2622_A Figure 1. Coronal CT image showing portal venous gas with pneumatosis of the stomach and the adjacent duodenum2622_B Figure 2. Transverse CT image showing portal venous gas with pneumatosis of the stomach and the adjacent duodenum

Pain Assessment after Short Course versus Long Course Palliative Radiation of Painful Bony Metastasis

Background: the most common cause of pain in cancer patients is bone metastases. Objective: to evaluate the different fractionation schedules. Patients and Methods: this is a prospective cross sectional study conducted at Ain-Shams University Hospitals and Nasser Institute Cancer Centre, to assess the equivalence of two fractionation regimens (20 Gy over 5 fractions versus 30 Gy over 10 fractions) as regard pain relief in painful bony metastases. Over 6 months fifty patients were assigned to either fraction arms using consecutive sampling. Results: both fractionation regimens were effective at palliating pain from bone metastases. Pain score was consistently going down from week 0 to week 12, although maximum benefit was reached earlier in the shorter arm (at week 8), both comparison groups leveled a favourable response at week 12. At 3 months, the observed overall response rate was 88% versus 84% and complete response rate was achieved in 44% versus 36% in both short- and long fractionation course respectively, with no statistical difference was found in terms of pain relief. With the median time to pain progression was 79.0 days for the short arm versus 77.0 days for the protracted arm. Conclusion: lower dose of radiotherapy may provide equivalent outcomes to higher ones in palliating bone pain. So, the the surrounding normal tissue role in pain process caused by bone metastases as well as the effect of radiation in this environment has to be furtherly investigated, which may lead to pain control augmentation.

Pain Assessment after Short Course versus Long Course Palliative Radiation of Painful Bony Metastasis

Pain Assessment after Short Course versus Long Course Palliative Radiation of Painful Bony Metastasis

Abstract B003: NRH:quinone oxidoreductase 2 (NQO2) and glutaminase (GLS) both play a role in large extracellular vesicles (LEV) formation in preclinical LNCaP-C4-2B prostate cancer model of progressive metastasis

Abstract Advanced-stage prostate cancer is characterized by osseous metastases whose establishment involves the dynamic interplay of factors and exchange of cellular contents by constituents of the tumor bony microenvironment. Among the factors that transport cellular cargoes and facilitate the transmission of signaling complexes for establishment of the bone metastatic lesions are large extracellular vesicles (LEVs), also known as large oncosomes. Information on the contents of LEVs and the mechanisms by which LEVs are formed and regulated is incomplete. In the course of studies aimed at elucidating the mechanisms of bony metastases using the LNCaP-C4-2B prostate cancer progression model, we show that the expression and cellular distribution of nicotinamide riboside: quinone oxidoreductase 2 (NQO2) and glutaminase (GLS, kidney type) both participate in the induction of membrane-localized oxidative stress and the formation of LEVs. The salient features of our findings are the following: The LNCaP model system exhibits gradually increasing oxidative stress levels as it progresses to the bone metastatic derivative C4-2B, while at the same time showing a progressive decrease in the expression level of NQO2. Reverse transcription PCR studies showed that NQO2 mRNA levels were unchanged between LNCaP and its metastatic derivatives C4, C4-2 and C4-2B. As a control, the expression level of the analogous enzyme NADP(H):quinone oxidoreductase 1 (NQO1) was also unchanged. These results suggested the possibility that the NQO2 enzyme in the bone metastatic C4-2B derivative could be localized elsewhere, possibly at an extracellular location. Further studies showed that a fraction of the NQO2 enzyme was associated with the detergent resistant membrane fraction of the C4-2B prostate cancer cells. Molecular modeling studies showed that the NQO2 enzyme had two caveolin-1 and NQO1 enzyme had one caveolin-1 binding sites. While the caveolin-1 binding site of NQO1 is buried inside the molecule and hence inaccessible to caveolin-1, one of the two binding sites available in NQO2 was external and accessible to caveolin-1. We have validated the specific interaction between NQO2 and caveolin-1 using deletion constructs of caveolin-1 fused with glutathione S-transferase (GST). Mitochondrial preparations of LNCaP, C4, C4-2, and C4-2B cells showed increasing level of expression of the GLS enzyme, suggesting a correlation between increased oxidative stress, glutaminase activity, and metastatic potential. Moreover, we found that the metastatic C4-2B derivative extruded LEVs in which the enzyme NQO2 and caveolae specific caveolin-1 could be visualized as cargo using double immunofluorescence studies. The extrusion of these LEVs could be inhibited by the GLS specific inhibitor BP-TES. Characteristically, curcumin was also found to inhibit the extrusion of these LEVs. This naturally occurring plant-based compound was shown earlier to inhibit prostate cancer bone metastasis in vivo using the C4-2B model. These results indicate a role for the NQO2 enzyme at the membrane level, possibly increasing the oxidative stress in a localized manner by lipid peroxidation. These results also suggest that a glutamine/GLS-mediated metabolic reprogramming in the LNCaP model system as it progresses toward the bone metastatic C4-2B is an integral component of the force driving the metastatic process. Based on the results of our studies, a combinatorial strategy using antimetastatic therapies such as nitrogen-containing bisphosphonates (NBPs) and anti-GLS therapy or, alternatively, a naturally occurring plant compound-based anti-NQO2 and anti-GLS therapy, could be considered for treating advanced prostate cancer patients with bone metastatic complications. Citation Format: Thambi Dorai, Ankeeta B. Shah, Faith Summers, Rajamma Mathew, Jing Huang, Tze-chen Hsieh, Joseph M. Wu. NRH:quinone oxidoreductase 2 (NQO2) and glutaminase (GLS) both play a role in large extracellular vesicles (LEV) formation in preclinical LNCaP-C4-2B prostate cancer model of progressive metastasis [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B003.

Comparison of 11C-choline Positron Emission Tomography/Computed Tomography (PET/CT) and Conventional Imaging for Detection of Recurrent Prostate Cancer.

We aimed to compare 11C-choline positron emission tomography/computed tomography (PET/CT) with conventional imaging, including pelvic magnetic resonance imaging (MRI), contrast-enhanced chest, abdomen, and pelvic computed tomography (CT), and bone scintigraphy, for prostate cancer restaging. Thirty patients (median prostate-specific antigen [PSA: 11.8 ng/mL]) with suspected recurrent prostate cancer following definitive treatment underwent 11C-choline PET/CT and conventional imaging, including pelvic MRI, contrast-enhanced chest, abdomen, and pelvic CT, and bone scintigraphy. The results were compared with regard to patient- and lesion-based diagnostic performance for local recurrence, and for lymph node and bony metastases using receiver operating characteristic (ROC) analysis and McNemar’s test. Documented local recurrence and node and bony metastases were present in 11 (36.7%), 10 (33.3%), and 17 (56.7%) cases, respectively, of the enrolled patients. Patient-based sensitivity / specificity / accuracy / area under the ROC curve for 11C-choline-PET/CT for diagnosing local recurrence were 90.9% / 94.7% / 93.3% / 0.975 and for conventional imaging were 90.9% / 100% / 96.7% / 1.0. Those who underwent 11C-choline-PET/CT for node metastasis were 90.0% / 95.0% / 93.3% / 0.925 and for conventional imaging were 70.0% / 95.0% / 86.7% / 0.905. Those who underwent 11C-choline-PET/CT for bone metastasis were 94.1% / 92.3% / 93.3% / 0.991 and who underwent conventional imaging were 94.1% / 84.6% / 90.0% / 0.982. No significant differences were observed among them. The lesion-based detection rate of 11C-choline PET/CT for local recurrences and node and bone metastases as compared to conventional imaging was 92.9% (13/14) vs. 92.9% (13/14); 87.1% (27/31) vs. 54.8% (17/31); and 96.9% (219/226) vs. 90.3% (204/226) respectively, with significant differences noted for detection of node and bone lesions (p=0.0044 and p=0.00030, respectively). 11C-choline-PET/CT is more accurate in the detection of recurrent prostate cancer nodes and bony metastatic lesions compared to conventional imaging and has the advantage of restaging the disease in a single step.

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

Low‐grade ovarian serous carcinoma metastasis to the maxilla

AbstractThe maxillofacial region is an uncommon site for metastases from distant primary tumours, representing only 1–2% of malignancies at this site. Such metastases usually present in the mandible rather than the maxilla. The most common sites of primary tumour are the breast, lung and kidney. We describe the clinical, radiological and histologic features of the first‐known case of a low‐grade serous carcinoma of the ovary metastasising to the posterior maxilla. Low‐grade serous carcinoma of the ovary is an uncommon entity and is biologically distinct from high‐grade serous carcinoma. Extra‐abdominal spread is uncommon and bony metastases are rare. Intraosseous metastases are often associated with disseminated disease and confer a poor prognosis.

Radiotherapy-induced anti-tumor immune response and immune-related adverse events in a case of recurrent nasopharyngeal carcinoma undergoing anti-PD-1 immunotherapy

BackgroundTreatment of recurrent nasopharyngeal carcinoma is a challenging clinical problem. We report the case of a 46 year old male showing excellent response and signs of immunostimulation following re-re-irradiation for recurrent nasopharyngeal carcinoma under systemic treatment with pembrolizumab.Case presentationPatient was first diagnosed with locoregionally advanced, non-keratinizing nasopharyngeal carcinoma in 2010. After achieving complete remission following induction chemotherapy and concurrent curative chemoradiation, the patient subsequently developed distant and locoregionally recurrent disease. He received various treatments (neck dissection, radiotherapy to a bony metastasis, palliative chemotherapy, stereotactic re-irradiation of local recurrence) before initiation of anti- PD-1 immunotherapy with pembrolizumab in January of 2016. Following marked local progression 6 months thereafter, we performed re-re-irradiation of the recurrent tumor after careful evaluation and treatment planning. While treatment was well tolerated, the patient subsequently developed marked clinical and radiological signs of immunostimulation with mucosal irritation and swelling of lacrimal and salivary glands as described in the report. Immunotherapy with pembrolizumab was reinitiated, with re- staging showing excellent response with regression of all tumorous lesions. At the time of this report, following near complete recovery of inflammatory symptoms, the patient remains in excellent condition and free from recurrence under treatment with pembrolizumab.ConclusionsTo our knowledge, we report the first observation of a combined effect of immunotherapy and radiotherapy in a patient with recurrent nasopharyngeal carcinoma. Demonstrating distinct signs of immunostimulation as well as excellent tumor response in a heavily pretreated patient progressing under anti-PD-1 immunotherapy, the case adds to the rising paradigm of an immunostimulatory effect of radiotherapy in patients undergoing treatment with immune checkpoint inhibitors.

Multiparametric Whole-body MRI with Diffusion-weighted Imaging and ADC Mapping for the Identification of Visceral and Osseous Metastases From Solid Tumors

The purpose of this study was to investigate the use of multiparametric, whole-body, diffusion-weighted imaging (WB-DWI) and apparent diffusion coefficient (ADC) maps with T2-weighted magnetic resonance imaging (MRI) at 3T for the detection and monitoring of metastatic disease in patients. Fifty-four participants (32 healthy subjects and 22 patients) were scanned with WB-DWI methods using a 3T MRI scanner. Axial, sagittal, or coronal fat-suppressed T2-weighted (T2WI), T1-weighted (T1WI), and DWI images were acquired. Total MRI acquisition and set-up time was approximately 45 minutes. Metastatic disease on MRI was confirmed based on T2WI characteristics. The number of lesions was established on computed tomography (CT) or positron emission tomography (PET-CT). Whole-body ADC maps and T2WI were constructed, and region-of-interests were drawn in normal and abnormal-appearing tissue for quantitative analysis. Statistical analysis was performed using a paired t tests and P < .05 was considered statistically significant. There were 91 metastatic lesions detected from the CT or PET-CT with a missed recurrent lesion in the prostate. Multiparametric WB-MRI had excellent sensitivity (96%) for detection of metastatic lesions compared to CT. ADC map values and the ADC ratio in metastatic bone lesions were significantly increased (P < .05) compared to normal bone. In soft tissue, ADC map values and ratios in metastatic lesions were decreased compared to normal soft tissue. We have demonstrated that multiparametric WB-MRI is feasible for oncologic staging to identify bony and visceral metastasis in breast, prostate, pancreatic, and colorectal cancers. WB-MRI can be tailored to fit the patient, such that an "individualized patient sequence" can be developed for a comprehensive evaluation for staging and response during treatment.

Impact of Magnetic Resonance Imaging on Gross Tumor Volume Delineation in Non-spine Bony Metastasis Treated With Stereotactic Body Radiation Therapy

This study investigates the inter-observer variability of contouring non-spine bone metastases using the planning CT alone vs. the addition of MRI T1 and T2 imaging sequences. 10 cases of non-spine bone metastases treated with SBRT at our institution were selected. The gross tumor volume (GTV) for each case was delineated by six SBRT radiation oncologists (RO) and one diagnostic radiologist (DR) on the treatment planning CT. After a minimum of three months, each case was re-contoured on the CT fused with a MRI T1 sequence followed by a MRI T2 sequence. STAPLE consensus contours were created from the RO volumes and inter-observer variability was measured using both κ agreement and the Dice coefficient (DSC). In total, 180 RO contours were analyzed within three datasets (CT, CT + MRI T1 and CT + MRI T1 + MRI T2). The mean GTV was 16.95 cm3 (range, 0.12-269.6 cm3). The RO κ agreement was 0.6129 based on CT alone, and significantly increased to 0.7045 in the CT + MRI T1 (P = .042) dataset and 0.7017 in the CT + MRI T1 + MRI T2 dataset (P = .048). The mean DSC in the CT alone dataset was 0.7047, and significantly increased to 0.7628 in the CT + MRI T1 dataset (P < .001) and 0.7544 in the CT + MRI T1 + MRI T2 dataset (P = .001). There were no statistical differences in RO κ agreement (P = .948) or mean DSC (P = .573) when comparing the CT + MRI T1 and CT + MRI T1 + MRI T2 datasets. The DSC agreement between DR and RO volumes was lowest (0.6887) in the CT alone dataset and significantly increased to 0.7398 in the CT + MRI T1 dataset (P = .003) and 0.7342 in the CT + MRI T1 + MRI T2 dataset (P = .008). The fusion of MRI T1 images to CT significantly reduced inter-observer variability amongst RO's in delineating non-spine bone metastases, and improved agreement between GTVs delineated by the RO to the DR.

CaPSURE update: Examining primary treatment and survival among men with prostate cancer and bony metastatic disease.

275 Background: New data is emerging to guide primary treatment of patients with metastatic (M+) disease. Among the CHAARTED and LATITUDE cohorts, 27.2% and 5% of patients with M+ disease had prior local therapy, respectively. This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry to examine survival among patients with M+ disease. Methods: CaPSURE is a registry of men diagnosed with prostate cancer. We examined sociodemographics, disease biology, primary therapy, and survival among patients who were diagnosed with cM+ disease or developed metastasis. We performed a multivariate Cox model to evaluate the association between timing of metastasis and prostate cancer specific mortality (PCSM), adjusted for age, primary treatment, and follow-up therapy. Results: Of the 14,753 patients diagnosed with prostate cancer from 1990-2016, 717(4.9%) had M+ disease. 328(2.2%) had cM+ disease and 389(2.6%) progressed to bony metastasis. For all patients with M+ disease, 490(68.3%) were &gt; = 65 yo, 627(87.4%) had Medicare, and 239(33.3%) had an annual income &lt; $30,000 (P &lt; 0.01). PSA at diagnosis was &gt; 20 ng/mL for 355(49.5%) and biopsy Gleason was 4+3 or 8 to 10 for 403(56.2%) (P &lt; 0.01). Among patients with cM+ disease, 49(14.9%) received primary local therapy and 279(85.1%) received primary hormonal therapy. Among patients who progressed to M+ disease, 258(66.3%) received primary local therapy and 131(33.7%) received primary hormonal therapy. The risk of PCSM was worse for patients with M+ disease who received hormonal therapy for primary treatment compared to patients who received combined local and hormonal therapy (HR 1.47 (95% CI 1.15 to 1.88), P &lt; .01). Timing of metastatic disease was not associated with PCSM. Primary treatment with hormonal therapy compared to local therapy was associated with higher risk of PCSM (HR 1.40 (95% CI 1.00-1.97), P = 0.05) for patients diagnosed with Gleason &gt; = 4+3 disease. Conclusions: In our analysis, patients with primary local therapy were examined as a subset of all patients with M+ disease. We observed that patients with cM+ disease have a worse prognosis then patients who develop M+ disease with antecedent primary local therapy.

Metastases-directed therapy (MDT) for oligometastatic prostate cancer.

375 Background: Stereotactic ablative radiotherapy (SABR) is emerging as a treatment option for patients with oligometastatic prostate cancer. The primary aim of this approach is to prolong disease free survival and delay the initiation of systemic therapies. This retrospective study is aimed to analyse local control, biochemical progression-free survival (b-PFS), toxicity and systemic therapy-free survival in a cohort of patients treated by a single clinician. Methods: Eighteen patients (26 lesions) in patients with relapsed oligometastatic prostate cancer ( 1-3 sites) were treated with SABR, delivered using both cyberknife and VMAT. Doses used were 24 Gy in 2 or 3 fractions for spine and 30 - 40 Gy in 3 fractions for lymph nodes and other bony metastases. All patients had either a Choline or PSMA- PET scan prior to treatment. Response was assessed with PSA testing and repeat scanning when feasible. CTCAE acute and late toxicity was prospectively recorded. Results: Mean age was 68. Previous treatments for the primary prostate cancer included surgery (7 patients), surgery and salvage prostate bed radiotherapy (6 patients), radical radiotherapy (4 patients) and cryotherapy (1 patient). Twelve patients had a single metastatic site, four patients had 2 sites and two patients had 3 sites. Six patients patients were treated with a short course of androgen deprivation therapy (ADT) in addition to SABR. All patients had a fall in PSA with a mean reduction of 75%. Median pre-SABR PSA was 1.83μg/L and median post-SABR PSA was 0.28μg/L. At a median follow-up of 14 months (range 2 - 28.5), 14 patients (78%) remained systemic therapy free. Three patients with a single pelvic lymph node metastases achieved a sustained undetectable PSA level. All 8 patients who had a post-treatment PET scan showed no residual activity at the treated site. One patient experienced G2 acute bowel toxicity, otherwise there was no toxicity above G1. Conclusions: MDT using SABR for relapsed prostate cancer is a safe treatment with promising results in terms of local control, b-PFS and delaying the initiation of systemic therapies. This minimally invasive approach has the potential to improve patients' quality of life, but requires further evaluation in randomised clinical trials.

Do patients with p16-positive oropharyngeal squamous cell carcinoma get more bone metastasis than p16-negative patients?

Oropharyngeal squamous cell carcinoma is thought to rarely metastasise to bone. This study hypothesised that in p16-positive disease there is a significant incidence of bony metastasis. This was an ambispective cohort review. All patients with oropharyngeal squamous cell carcinoma diagnosed and treated at one centre were included. A total of 180 consecutive patients were identified over 5 years. Fifteen patients were excluded because of lack of p16 status, none of whom had bony metastasis. The final analysis included 165 patients: 48 (29.09 per cent) in the p16-negative group and 117 (70.91 per cent) in the p16-positive group. Ten patients (8.55 per cent) in the p16-positive group developed bony metastasis, compared with zero in the p16-negative group; this difference was statistically significant (p = 0.036). Expression of p16 was associated with an increased incidence in bony metastasis in this cohort. This is the first study to explore this specific question.

Carcinoma of gall bladder: Demographic and clinicopathological profile in Indian patients

Aim of the Study: The aim of this study is to evaluate the demographic and clinicopathological profile of the patients with gallbladder cancer (GBC). Materials and Methods: A total of 68 diagnosed cases of GBC were taken in the study during the study period from January 2016 to December 2017. A detail questionnaire was filled through the counseling to take demographic profile including socioeconomic status, nonclinical characteristics, dietary, and other risk factors apart from clinicopathological profile of patients. Results: We found most of the patients were females with median age 51.8 years. More than half of them were postmenopausal (56.60%), and high parity was seen in 39.62% of females. Obesity was associated factor mainly in females (28/53), and none of the males were obese. Nearly 83.82% (57/68) of patients had advanced stage disease, with metastatic disease in 72.06% (49/68) patients. Majority of the patients had at least two sites of metastasis (73.47%), with liver (57.14%), omentum (40.82%), and nonregional lymph nodes (53.06%) being common sites of dissemination. Bony metastasis, being rare in literature, was found in 6 (12.24%) of patients, most of them developed it later during the disease course. Conclusion: Majority of the patients was female within the age group of 41–60 years, associated with gallstones and had advanced disease. We did not find greater impact of diet on the incidence as vegans and nonvegans were almost equally divided in our study. A high index of suspicion and health education seems to be the only answers available for early detection and improvement of survival.

Hyperplastic hematopoietic bone marrow of the spine mimicking spinal metastasis: A case report and review of literature

Magnetic resonance imaging (MRI) has a high sensitivity for detecting metastatic bone tumors. However, distinguishing metastasis from benign lesions can be difficult. We report a case of hyperplastic hematopoietic bone marrow of the spine mimicking spinal metastasis. A 73-year-old male presented to the orthopaedic clinic with worsening back pain following a fall. Initial radiographs demonstrated a compression fracture of the T11, L1, and L2 vertebral body. MRI showed multiple scattered hypointense foci within the lumbar spine suspicious for osseous metastases, with old-healed fractures at T11, L1, and L2. Whole spine imaging was then performed demonstrating similar marrow signal abnormality in the cervical and thoracic spine. Initial suspicion for a pathological fracture secondary to bony metastasis was strong. Subsequent screen for malignancy was negative. Open biopsy was done on the T4 vertebra, and the histopathological diagnosis was spinal hyperplastic hematopoietic bone marrow. This condition is characterized by reconversion of fatty marrow to hematopoietic marrow, which can occur in chronic anemia, obesity, heavy smokers or following trauma. This case illustrates a rare differential diagnosis for suspected metastatic bone tumor, and our report discusses the important radiologic differences between both conditions.

Extraspinal Percutaneous Osteoplasty for the Treatment of Painful Bony Metastasis.

BackgroundExtraspinal percutaneous osteoplasties (POPs) are novel techniques for the treatment of painful bony metastasis, which is often the cause of both persistent and incidental breakthrough pain. This retrospective study explored the efficacy and complications of extraspinal POPs.MethodsThe origin of the cancer metastasis, performed POP sites, necessity of adjacent joint injections, pain and Karnofsky Performance Scale (KPS) scores, complications related to the POPs, and life expectancy were evaluated from the medical records from 2009 to 2016.ResultsA total of 47 (M/F = 28/19) patients had received 54 POPs, including costoplasty, scapuloplasty, ilioplasty, humeroplasty, ischioplasty, femoroplasty, sternoplasty, and puboplasty, in order of frequency. The most common sites for the origin of the cancer, in order of frequency, were the lung, liver, breast, colon, and kidney. All patients receiving POPs including scapuloplasty, ilioplasty, humeroplasty, and femoroplasty needed adjacent joint injections before or after the POPs. Pain due to metastatic lesions was reduced significantly immediately after the POPs and the reduction was sustained until the end of their lives. The median KPS was increased from 35.4% to 67.7% immediately after the POPs. There were no complications related to the procedures. The mean life expectancy after performing the POPs, for 35 patients which died afterwards, was 99.3 days, ranging from 1 to 767 days.ConclusionEven though pain in the isolated POP sites may be difficult to measure due to overlapping systemic pain, the POPs provided immediate local pain relief, and the patients showed better physical performance without procedure-related complications.

Spinal tumours: diagnosis, clinical presentation and principles of treatment

Spinal tumours can be categorized as primary or metastatic. Primary neoplasms of the spine are rare and constitute less than 5% of bony tumours accounting for 2.5–8.5 affected individuals per 100,000 people per year. Primary spinal tumours can be divided into benign and malignant. Metastatic disease of the spine is much more common with 40–80% of patients who die of cancer having bony metastases at the time of their death and the spine being one of the most common sites of metastasis. A further subdivision in both benign and malignant disease is anatomical – that of bony and intradural components, though the focus in the current review is on the bony involvement. A key presenting feature is pain, with characteristic features which will be discussed in detail. Meticulous clinical assessment and work-up with early recognition and diagnosis can significantly improve morbidity and be curative in benign disease. Despite advances in treatment, the overall prognosis in malignant spinal disease, either metastatic or primary is relatively poor. This chapter provides a broad overview of neoplastic conditions looking at presenting signs and symptoms, differentials, clinical assessment and principles of management. This should allow for prompt recognition and expedite treatment.