Evidence Of Visceral Metastases Research Articles

Phase II clinical trial of sequential treatment with systemic chemotherapy and intraperitoneal paclitaxel for gastric and gastroesophageal junction peritoneal carcinomatosis - STOPGAP trial

BackgroundStudies from Asia indicate that normothermic intraperitoneal chemotherapy (NIPEC) may confer survival benefit in patients with gastric peritoneal carcinomatosis (PC). However, data regarding this approach is lacking in western population. The current STOPGAP trial is intended to assess 1-year progression-free survival benefit of sequential systemic chemotherapy and paclitaxel NIPEC in patients with gastric/ gastroesophageal junction (GEJ) adenocarcinoma PC.MethodsThis is a prospective, single center, single arm, phase II investigator-initiated clinical trial. Patients with histologically proven gastric/GEJ (Siewert 3) adenocarcinoma with positive peritoneal cytology or PC will be eligible to participate after three months of standard of care systemic chemotherapy and with no evidence of visceral metastasis on restaging scans. The primary treatment is iterative paclitaxel NIPEC with systemic paclitaxel and 5-fluorouracil, which will be administered on days1 and 8 and repeated every three weeks for 4 cycles. Patients will undergo diagnostic laparoscopy both before and after NIPEC to assess peritoneal cancer index (PCI). Patients with PCI less than or equal to 10 in whom complete cytoreduction (CRS) is feasible may opt to undergo CRS with heated intraperitoneal chemotherapy (HIPEC). The primary endpoint is 1-year progression free survival and secondary endpoints are overall survival and patient reported quality of life outcomes measured by EuroQol- 5 dimensions-5 level (EuroQol-5D-5L) questionnaire.DiscussionIf the sequential approach of systemic chemotherapy followed by paclitaxel NIPEC proves beneficial, then this approach could be used in larger, muti-institutional randomized clinical trial of gastric PC.Trial RegistrationThe trial was registered on 21/02/2021, under clinical trials.gov; Identifier: NCT04762953.

Abstract 3054: Synergistic activity of DNA damage response kinase inhibitors in combination with the targeted alpha therapy radium-223 dichloride for metastatic castration-resistant prostate cancer

Abstract Radium-223 dichloride (Ra-223, Xofigo®) is the first approved α-particle-emitting radionuclide for the treatment of symptomatic bone metastases in patients with castration-resistant prostate cancer (CRPC) with no known evidence of visceral metastases. Ra-223 is a calcium-mimetic that preferentially binds with the bone mineral hydroxyapatite at areas of high bone turnover, such as bone metastases. This highly localized radiotherapy causes a high frequency of unrepairable double-stranded DNA breaks (DSBs), resulting in a potent antitumor effect on bone metastases. Recent evidence has suggested that patients with mutations in the DNA damage response pathway (DDR), may have differential outcomes to Ra-223 treatment (1).DDR comprises a dynamic network of signaling pathways for the maintenance of genomic integrity. Ataxia telangiectasia mutated (ATM) and Rad3-related (ATR) are critical proteins which orchestrate the DDR and their activation is dependent on the type of DNA lesion. ATM is the primary responder to DSBs whilst ATR is activated by a range of lesions including single strand DNA structures at resected ends of DBSs and after replication fork stalling. In this study, we evaluated the impact of combining DDR kinase inhibitors with Ra-223 to investigate whether a greater radiosensitization response occurs in comparison to standard X-rays in PC3 and DU145 human prostate cell lines and normal prostate epithelial RWPE-1 cells. Cell assays including clonogenic survival, DNA damage assays and flow cytometry were used to assess the effect of DDR kinase inhibitors in combination with ionizing radiation. Cells were pre-treated with DDR inhibitors one-hour before exposure to 2Gy X-rays or an equivalent dose of 0.25Gy Ra-223. Our data show that, in all prostate models, DDR kinase inhibitors in combination with Ra-223 significantly enhanced radiosensitivity (p<0.005) response in comparison to combined treatment with X-rays. Furthermore, a greater quantity of residual DSBs at 24 hours post combination treatment was observed after Ra-223 exposure in comparison to X-ray exposure (p<0.001). Promisingly, this combined treatment had minimal effect on RWPE-1 normal cells. Our findings strongly support the combination of DNA damage induction by Ra-223 with DDR kinase inhibitors as a novel potential treatment option for mCRPC patients in order to improve clinical outcome. {{References}}:1.Velho PI, Qazi F, Hassan S, et al. Efficacy of Radium-223 in Bone-metastatic Castration-resistant Prostate Cancer with and Without Homologous Repair Gene Defects. European Urology. 2019; 76: 170-176. Citation Format: Victoria L. Dunne, Timothy Wright, Francisco Liberal, Joe M. O'Sullivan, Kevin M. Prise. Synergistic activity of DNA damage response kinase inhibitors in combination with the targeted alpha therapy radium-223 dichloride for metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3054.

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II.

The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.

2722 Thinking With the Gut: An Unfortunate Case of Metastatic Gastric Cancer

INTRODUCTION: Metastatic brain tumors represent 20-40% of intracranial neoplasms [Table 1]. Although rare, the incidence of brain metastasis from the gastrointestinal (GI) tract has increased likely secondary to prolonged survival of patients with GI cancers. Symptoms of metastatic spread parallels space-occupying lesions in brain: confusion, headache, visual disturbances, nausea, vomiting, altered mental status, gait abnormalities, seizures, and decreased consciousness. Current literature estimates 0.63% of gastric adenocarcinoma (GA) cases metastasize to the brain1. Here, we present an unusual case of metastatic brain spread of GA. CASE DESCRIPTION/METHODS: 59-year-old male with history of hypertension, tobacco use, GERD, and gastric cancer who presented with a one-week history of headaches, nausea and vomiting, and decreased visual acuity. His gastric cancer had previously been treated with neoadjuvant chemotherapy, radiation and partial esophagectomy with repeat screening via computed tomography (CT). A CT of his head showed vasogenic edema in the right frontal lobe, raising concern for metastatic disease versus primary CNS lesion [Figure 1]. A magnetic resonance imaging (MRI) brain showed an enhancing mass in the anterior-inferior right frontal lobe with metastatic disease as well as leptomeningeal carcinomatosis [Figure 2]. He underwent right frontal burr-hole for stereotactic biopsy of the right frontal tumor. Pathology was consistent with metastatic adenocarcinoma. He was started on IV steroids and began whole brain radiation therapy. He was not a surgical candidate and was unstable for chemotherapy. His family transitioned him to comfort care measures after which he shortly passed. DISCUSSION: Gastric cancer is the fourth most common cancer worldwide and the second most common cause of cancer-related death. Current literature estimates GA incidence rate to be 6.7/100,000 persons with a mortality rate of 3.4/100,000 persons in the United States. Risk factors include H. pylori, male sex, Asian/Pacific island ethnicity, obesity, smoking, and a diet rich in smoked, salted, pickled foods. Our patient demonstrated an unusual case of metastatic GA without evidence of visceral metastases. His case was further complicated as he had screening CT scans at six month intervals which had been within normal limits until his presentation. His case unfortunately demonstrates the ominous prognosis of patients with brain metastasis, prompting the need for increased surveillance and brain imaging.

Radium-223 for the treatment of bone metastases in castration-resistant prostate cancer: when and why.

Radium-223 dichloride (223Ra) is the first, recently approved, α-particle-emitting radiopharmaceutical for the treatment of patients with bone metastases in castration-resistant prostate cancer (CRPC) and no evidence of visceral metastases. We explored MEDLINE, relevant congresses, and websites for data on 223Ra and prostate cancer therapies, focusing on therapeutic strategies and timing, bone metastases, and diagnostic assessment. 223Ra represents the only bone-targeting agent that has significantly extended patients' overall survival while reducing pain and symptomatic skeletal events. Unlike other radiopharmaceuticals, such as strontium-89 and samarium-153 EDTMP, 223Ra (11.4-days half-life) has shown a high biological efficiency mainly due to its short penetration range. These features potentially allow reduced bone marrow toxicity and limit undue exposure. 223Ra has been validated under the product name Xofigo® by the US Food and Drug Administration and the European Medicines Agency. Patient selection, management, and treatment sequencing is recommended to be discussed in the context of a multidisciplinary environment, including oncology, urology, nuclear medicine, and radiation therapy physicians. No consensus has been achieved regarding the optimal timing and its administration as single agent or in combination with zoledronic acid or chemotherapy, so far. This review aims to provide a rationale for the use of 223Ra in treating metastases from CRPC, highlighting the crucial role of a multidisciplinary approach, the disputed inclusion and exclusion criteria on the basis of agencies regulations, and the value of diagnostics for therapy assessment.

An unusual case of esophageal adenocarcinoma presenting with disseminated intravascular coagulation (DIC) as a result of carcinomatosis of the bone marrow

We describe a rare case of esophageal adenocarcinoma presenting with carcinomatosis of the bone marrow resulting in disseminated intravascular coagulation (DIC). A 73-year-old male presented with fatigue, night sweats, and easy bruising. Laboratory evaluation showed severe anemia, thrombocytopenia, and a coagulopathy consistent with DIC. Bone marrow biopsy demonstrated markedly hypocellular marrow with involvement of metastatic adenocarcinoma. Upper endoscopy revealed a stenotic lesion at the gastroesophageal junction, and biopsies confirmed esophageal adenocarcinoma. Imaging studies showed no evidence of visceral metastases. DIC was attributed to diffuse bone marrow involvement of the primary esophageal cancer. The patient received intensive supportive care for his DIC followed by first-line chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). Treatment of the underlying malignancy resulted in stabilization of his DIC. This is the first reported case of esophageal adenocarcinoma with disseminated carcinomatosis of the bone marrow leading to DIC. We also discuss the prevalence and significance of bone marrow micrometastases in esophageal cancers as well as the association and clinical implications of DIC in solid tumor malignancies.

De novo metastatic prostate cancer: Patterns of PSA testing prediagnosis and disease characteristics.

271 Background: A small proportion of men with prostate cancer (PCa) will present with metastatic disease at first presentation, termed de novo metastatic PCa. PSA screening is not a national policy, yet PSA testing is commonly performed and national guidelines are available to guide subsequent management. We sought to investigate this group of men to determine if prior PSA testing had been previously performed, and if elevated, to determine if appropriate referrals were being made. We also sought to further characterise and analyse associated risk factors. Methods: A retrospective review of pts who presented with de novometastatic PCa over a three year period was performed in three cancer centres in Ireland. Characteristics such as demographics, Gleason score, symptoms at presentation and disease volume (high v low) were obtained. PSA results done in the primary care for a period of 12-24 months and > 24 months prior to diagnosis were recorded. Results: 100 pts with de novo metastatic PCa were identified between 2013 and 2015. Median age at diagnosis was 72 years (49-90), 77 pts (77%) presented with high volume disease, 11 pts (11%) had evidence of visceral metastasis with a median age of 62 years (51-72). Median PSA level at diagnosis was 106, and 91% of pts (n = 74) had a Gleason score of ≥ 8. Symptoms at presentation were evaluable in 88 pts with the majority of pts presenting with pain (n = 49, 55.6%) and lower urinary tract symptoms (n = 33, 37.5%). 22 pts (22%) had a PSA level done within 12-24 months prior to diagnosis which was higher than 4.0 ng/ml in 18 pts (82%). 57 pts (57%) had a PSA level done over 24 months prior to diagnosis which was higher than 4.0 ng/ml in 35 pts (61.4%), PSA measurement was only repeated in 18 pts (51%) out of 35 pts with high PSA levels prior to diagnosis. Having elevated PSA levels over 4.0 ng/ml within 12-24 months and over 24 months prior to diagnosis was not associated high volume metastatic disease (P = 0.88). Conclusions: A sizeable proportion of pts diagnosed with de novo metastatic PCa had PSA measurements performed more than one year prior to diagnosis which was elevated. Optimization and adherence to national guidelines regarding PSA testing is needed to decrease the number of pts diagnosed with de novo disease.

Microangiopathic hemolytic anemia associated with metastatic breast cancer: case report and literature review.

IntroductionMicroangiopathic hemolytic anemia (MAHA) is a mechanical hemolytic anemia characterized by the emergence of fragmented red cells in peripheral blood. Here, we report a case of breast cancer associated with cancer-related (CR)-MAHA along with a literature review.Case descriptionThe patient was a 54-year-old woman who made an emergency visit to our hospital because of low back pain, shoulder pain, visual impairment, and anemia. She was diagnosed with stage IV, ER-positive, PgR-positive, HER2-negative left breast cancer (invasive lobular carcinoma), with left axillary adenopathy, metastasis to the soft tissue of the orbital region, multiple bone metastases, pleural dissemination, and metastasis to the stomach and para-aortic lymph nodes. Chemotherapy was initiated successfully; tumor marker levels normalized and the visceral metastases almost disappeared. Hormone therapy was administered for maintenance. Two and a half years later, rapid elevation in tumor marker levels and severe anemia were noted, and fragmented red cells and poikilocytes emerged in the peripheral blood. Positron emission tomography–computed tomography and bone scintigraphy revealed multiple bone metastases, but no evidence of visceral metastasis. CR-MAHA associated with multiple bone metastases was diagnosed, and Paclitaxel chemotherapy was initiated with frequent blood transfusions. Her anemia gradually improved, with a decrease in tumor marker levels and the number of blood transfusions. Three months later, tumor marker levels increased again. Because the anemia was also exacerbated, chemotherapy was changed to eribulin. Tumor marker levels temporally decreased, and the anemia tended to improve, but 3 months later, the levels were elevated again and the anemia was exacerbated. A switch to another regimen was planned, but best supportive care was chosen instead because of rapid deterioration of liver function. The patient died a month later.Discussion and evaluationCR-MAHA is thought to have a different pathologic mechanism from TTP or HUS. Although CR-MAHA is a clinical condition associated with a very poor prognosis, we consider it controllable for long period by rapid introduction of chemotherapy in many cases.ConclusionsCR-MAHA is a nearly oncologic emergency that medical oncologists need to be able to recognize even though it rarely occurs in breast cancer.

Abstract P1-13-06: Impact of visceral metastases on treatment patterns for hormone-receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (mBC)

Abstract Introduction: Guidelines recommend reserving chemotherapy (CT) for HR+/HER2- mBC until either endocrine-based therapy (ET) is no longer effective or for patients with visceral crisis or need for rapid tumor control. The extent to which visceral metastases (VM), regardless of whether they are contributing to visceral crisis, impact real-world treatment patterns in mBC is not well understood. This retrospective analysis characterizes treatment patterns with ET and CT among HR+/HER2- mBC patients stratified by presence of VM. Methods: Postmenopausal women (age ≥50 years) diagnosed with HR+/HER2- mBC were identified from the MarketScan® database (2002Q3-2012Q2). Patients who initiated ET without CT for mBC were followed until transition to CT, discontinuation of ET (>90 days without evidence of ET), or end of data or insurance eligibility. Upon initiation of each line of therapy, patient characteristics including age, number of metastatic sites, and presence of VM were compared between those receiving ET and those receiving CT. The number of lines of ET received before CT, and the total duration of ET were described for patients with and without VM. Results: Of the 19,120 patients who initiated treatment for mBC, 5,418 received 2nd-line treatment and 1,471 received 3rd-line treatment. In each of these 3 lines, the corresponding numbers of patients receiving CT were 7,575 (40%), 2,397 (44%) and 650 (44%). Among the patients who received CT in each line, the majority did so without evidence of VM: 5,821 (77%), 1,511 (63%) and 435 (67%), in the 1st, 2nd and 3rd lines, respectively. Within each line, the average patient receiving CT was approximately 3 to 5 years younger and had 0.02-0.29 more metastatic sites, compared with the average patient receiving ET. Among the 11,545 patients who initiated 1st-line ET, 9,315 (81%) did not have evidence of VM. Patients with versus without VM upon initiation of 1st-line ET received similar average numbers of lines of ET (1.32 versus 1.37 lines). However, the median time prior to transition to CT, discontinuation of ET, or loss to follow-up was shorter for patients with VM compared to those without VM (5 months versus 10 months). In addition, patients with VM appeared to have shorter durations of ET at each line compared with patients without VM (Table). Conclusions: Although the present analysis could not distinguish visceral crisis from the broader group of patients with visceral metastases, it is notable that a large majority of patients receiving CT did so without evidence of VM. This indicates an unmet need during the study period (2002-2012) for effective disease control among patients without VM for whom CT was not a preferred option. Table. Durations (months) of Endocrine Therapy Total number of lines of ET observed, with and without VM One LineTwo lines≥ Three linesLine of ET / patient groupVMWithout VMVMWithout VMVMWithout VMAll Patients, median (IQR)3 (1-8)6 (2-16)11 (6-23)15 (8-27)23 (14-35)26 (16-41)First line3 (1-8)6 (2-16)6 (3-15)7 (3-16)8 (3-17)9 (3-17)Second line--3 (1-6)4 (2-10)6 (3-12)5 (3-11)Third line----3 (1-5)4 (2-9)VM = visceral metastases, IQR = interquartile range Citation Format: James Signorovitch, Jenny Wang, Ruo-Ding Tan, Darren Thomason, Andrew Kageleiry, Elyse Swallow. Impact of visceral metastases on treatment patterns for hormone-receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (mBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-13-06.

The Prognostic Role of Pretreatment 18F-FDG (PET/CT) Maximum Standardized Uptake Value in Multiple or Oligometastatic Breast Cancer Patients

Purpose: To determine the prognostic role of pretreatment F-18FDG PET/CT maximum standardized uptake value (SUVmax) in metastatic breast cancer (MBC) patients and its correlation with clinicopathological parameters. Materials and Methods: The pretreatment 18FDG-PET-CT SUVmax in MBC patients was compared with clinicopathological parameters. The prognostic value of pretreatment SUVmax for progression free survival (PFS) and overall survival (OS) were assessed using log rank test and cox regression analysis. Results: Overall, 100 patients (77%) had evidence of visceral metastases while 30 patients (23%) had oligometastatic disease confined to bones only. The receiver operator curve (ROC) demonstrated that SUVmax of 4.4 and 7.7 to be the cutoff value for predicting PFS in patients with oligometastasis to bones and multiple metastatic disease respectively. Patients with bone oligometastasis SUVmax of >4.4 had a significantly shorter OS [Hazard ratio (HR 3.2)] 4.4 (P 7.7.On Cox regression analysis, the SUVmax category was the only factor correlated with both PFS (HR=4.5, 95% C I 3-6.8, P<0. 0001) and OS (HR=3.2, 95% C I 2.2-4.9, P<0. 0001) in patients with multiple metastasis. Conclusions: The pretreatment 18FDG-PET-CT SUVmax showed a statistically significant association with different clinicopathological prognostic factors. In addition, it may be considered as a potential independent prognostic indicator of clinical outcomes in metastatic breast cancer. Keywords 18FDG PET/CT SUVmax; Metastatic breast cancer

Oral malignant melanoma: A report of two cases with BRAF molecular analysis.

Primary oral malignant melanoma is a rare condition, accounting for 1.3–1.4% of all melanomas, usually presenting with an aggressive clinical behavior. The present study reports the clinicopathological findings of two cases of oral malignant melanoma and discusses the epidemiology, diagnosis and current therapeutic approaches for this uncommon condition. In the first case the patient presented with a pigmented lesion located on the lower mucosal lip. The patient showed no nodal metastases and therefore, underwent a wedge resection. After seven months, the patient presented with neck lymph nodes and multiple visceral metastases. Molecular analysis of BRAF, using a pyrosequencing approach, revealed the presence of BRAF V600E mutation. The patient developed multiple visceral metastases, but refused treatment and was lost to follow-up. In the second case, no BRAF V600E mutation was found, but the patient exhibited a pigmented patch in the lower gingival mucosa, which was excised by surgical treatment. The patient was followed up by an oncologist, but did not undergo an additional therapy and is currently alive with no evidence of visceral metastases at one year following the diagnosis.

Predicting Survival for Surgery of Metastatic Spinal Cord Compression in Prostate Cancer

We retrospectively analyzed prognostic factors for survival in patients with prostate cancer operated for metastatic spinal cord compression. The aim was to obtain a clinical score for prediction of survival after surgery. Survival prognosis is important when deciding about treatment of patients with metastatic spinal cord compression. The criteria for identifying patients with prostate cancer who may benefit from surgical treatment are unclear. The study comprised 68 consecutive patients with prostate cancer operated for metastatic spinal cord compression at Umeå University Hospital, Sweden. The indication for surgery was neurological deficit; 53 patients had hormone-refractory prostate cancer and 15 patients had previously untreated, hormone-naïve prostate cancer. In 42 patients, posterior decompression was performed and 26 patients were operated with posterior decompression and stabilization. A new score for prediction of survival was developed on the basis of the results of survival analyses. The score includes hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum prostate-specific antigen (PSA). The total scores ranged from 0 to 6. Three prognostic groups were formulated: group A (n = 32) with scores 0-1; group B (n = 23) with scores 2-4, and group C (n = 12) with scores 5-6. The median overall survival was 3 (0.3-20) months in group A, 16 (1.8-59) months in group B, and more than half (7 of 12) of patients were still alive in group C. We present a new prognostic score for predicting survival of patients with prostate cancer after surgery for metastatic spinal cord compression. The score is easy to apply in clinical practice and may be used as additional support when making decision about treatment.

TomoTherapy Based IMRT for Breast Cancer with Skull Metastases

Introduction: A 59 year old lady presented 15 years ago with grade 3 invasive ductal breast carcinoma T2N1M0, ER positive and Her2 negative disease, and was treated with curative intent. Twelve years later she presented with mediastinal metastasis with superior venacaval obstruction and bone disease. She received radiotherapy, oral ibandronate and different hormonal treatments over the next few years to control the cancer with no evidence of visceral metastasis. In March 2010 she had scalp pain alone and elevation of Ca 15.3.

Evaluation and Modification of the Tomita Score in 217 Patients with Vertebral Metastases

The Tomita prognosis score consists of thefollowing 3 parameters: growth behavior, evidence ofvisceral metastases, and/or evidence of bony metastases.Methods: 217 consecutive patients, surgicallytreated for vertebral metastases of different entities,were studied retrospectively. The score according toTomita was determined. Results: In the study group, theTomita score showed significant results for the estimationof life expectancy of the different prognostic groups(p < 0.0001), but the analysis showed a low reliability, i.e.correlation between predicted prognosis and real survival.A modified division of the patients based on thetotal sum of points allowed a significant separation (p <0.0001) of patients into 2 prognostic groups with a realsurvival of more or less than 12 months. Conclusion: Inour study, the original Tomita score was not reliable topredict the life expectancy of cancer patients with spinalmetastases. Our modification allows a significant differentiationof patients with spinal metastases with a prognosisof more or less than 12 months.

The Addition of Tamoxifen to Dacarbazine and Cisplatin in Metastatic Malignant Melanoma

Based on the reports of substantial improvement in the response rate w ith the addition of tamoxifen to a multiagent chemotherapy regimen for metastatic melanoma, Southwest Oncology Group (SWOG)-8921 was initiated. A prior regimen (SWOG-8804) of dacarbazine (DTIC) 750 mg/m(2) i.v. day 1 and cisplatin 100 mg/m(2) day 1 repeated every 3 weeks produced a 13% response rate in patients with metastatic melanoma without brain metastasis. SWOG-8921 using identical chemotherapy and schedule added tamoxifen 10 mg twice daily. There were 55 eligible patients registered, median age 52, with 37 men and 18 women. Fifty (91%) patients had evidence of visceral metastasis at registration. There were 10 responders (2 complete and 8 partial responses) for an 18% response rate (95% CI, 9-31%). The response rate in women was 28% (95% CI, 10-53%; in men, 14% (95% CI, 5-29%). Tamoxifen has produced a small increase in the response rate when added to the present combination and schedule of chemotherapy. Further Phase III trials will be necessary to assess whether there is a statistical advantage to the use of tamoxifen when combined with chemotherapy and whether there are statistical differences between men and women.

Avian Keratoacanthoma (Dermal Squamous Cell Carcinoma) in Broiler Chicken Carcasses

Multiple lesions of dermal squamous cell carcinoma are found at a low frequency (0.04%) in the carcasses of young meat-type chickens at slaughter. For this study, affected carcasses (n = 308) were removed from the processing line, and lesions were characterized by size, distribution, and morphology. Carcasses were also sexed and examined for evidence of metastasis. Nodular (n = 297) and ulcerative (n = 1,707) lesions were counted and examined. Most lesions were present in the pectoral, dorsopelvic, and femoral feather tracts. Few lesions (n = 11) were found in wing tracts. Mean diameter was 5.4 mm for ulcerative lesions and 3.1 mm for nodular lesions. Histologic sections of ulcerative (n = 579) and nodular (n = 113) lesions were examined. Small nodular lesions originated from hyperplastic feather follicle epithelium. Nodules contained keratin-filled cysts lined by squamous epithelium that were associated with isolated islands and infiltrating cords of dermal keratinocytes. Loss of surface epithelium resulted in noduloulcerative and ulcerative lesions. Invasion of underlying skeletal muscle and evidence of visceral metastasis were not present, but invasion through elastic laminae and into the subcutis was present in 20.5% (134/654) of the lesions examined. The nodular lesions in these carcasses were morphologically similar to early nodular lesions previously described in live chickens as avian keratoacanthomas. A retrospective study compared selected production parameters and disease condemnations to the prevalence of squamous cell carcinoma in 665 flocks of broiler chickens. There was a positive correlation (P < 0.0001) with the occurrence of airsacculitis but a negative correlation with increased age and condemnations for leukosis (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)