Synchronous Lung Metastases Research Articles

Bone Metastases in Follicular Carcinoma of Thyroid.

Though the association between follicular carcinoma and bone metastasis is well established, the site-wise distribution is not known. One hundred seventy-three patients of follicular carcinoma presenting between 2003 and 2011 were selected from 1093 patients of follicular lesions presenting at a single institution. Of these, 59 (34%) with bone metastasis were included in the study. Fifty of the 59 patients (84.7%) had metastasis at presentation, while 9 developed bone metastasis during follow-up. Sixty-one percent had solitary metastasis, 15 (25.4%) had multiple bone involvement, while 8 patients (13.6%) had synchronous lung metastasis. Overall, the spine was the commonest site of bone metastases, seen in 20 patients (33.9%), followed by the pelvis, skull, long bones and sternum. Bone metastasis is a known phenomenon in follicular carcinoma. The spine is the commonest site followed by the pelvis.

EGFR Inhibition in a Pretreated Sacral Chordoma: A Role for Erlotinib? Case Report and a Brief Review of Literature.

We describe the case of a 69-year old male with an EGFR- positive Imatinib refractory sacral chordoma with synchronous lung metastases, treated with erlotinib, a first-generation EGFR inhibitor. After disease progression following first-line Imatinib and a combination therapy with everolimus plus metformin, we made a challenge with an EGFR tyrosine kinase inhibitor (EGFR TKI), erlotinib. Despite a brief clinical benefit, the patient presented a rapid clinical deterioration leading to death, after 8 weeks of treatment.

Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer

BackgroundPatients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging.Patients and methodsHere, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of 5 years. The chest wall metastasis was caused by needle tract seeding, implying a known time of onset. Using whole genome sequencing data from primary and metastatic sites we inferred the complete chronology of the cancer by exploiting the time of needle tract seeding as an in vivo ‘stopwatch’. This approach allowed us to follow the progression of the disease back in time, dating each ancestral node of the phylogenetic tree in the past history of the tumour. We used a Bayesian phylogenomic approach, which accounts for possible dynamic changes in mutational rate, to reconstruct the phylogenetic tree and effectively ‘carbon date’ the malignant progression.ResultsThe primary colon cancer emerged between 5 and 8 years before the clinical diagnosis. The primary tumour metastasized to the lung and the thyroid within a year from its onset. The thyroid lesion presented as a tumour-to-tumour deposit within a benign Hurthle adenoma. Despite rapid metastatic progression from the primary tumour, the patient showed an indolent disease course. Primary cancer and metastases were microsatellite stable and displayed low chromosomal instability. Neo-antigen analysis suggested minimal immunogenicity.ConclusionOur data provide the first in vivo experimental evidence documenting the timing of metastatic progression in CRC and suggest that genomic instability might be more important than the metastatic potential of the primary cancer in dictating CRC fate.

Stage IV colorectal cancer primary site and patterns of distant metastasis

BackgroundAlthough colorectal cancer (CRC) usually metastasizes to the liver and/or lungs, factors influencing the anatomic pattern of metastases remain poorly understood. MethodsWe assessed the relationship between primary CRC site and pattern of synchronous metastasis among 1202 individuals diagnosed with incident metastatic CRC between 2010 and 2014 and identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between primary tumor site and synchronous metastatic pattern. ResultsCompared to patients with proximal colon primaries, patients with rectal primaries were more likely to present with lungs-only or liver and lungs metastases versus liver-only metastases (ORlungs–onlyvs.liver-only: 2.39, 95% CI: 1.35–4.24, ORliver+lungsvs.liver-only: 2.20, 95% CI: 1.46–3.32). ConclusionThese findings suggest that patients with rectal primaries are more likely than patients with colon primaries to present with synchronous lung metastases.

Renal cell carcinoma with contralateral synchronous adrenal and lung metastasis: A rare case report

Renal cell carcinomas have propensity to metastasise to almost any organ. About 4.7–10.0% of these cases present with ipsilateral adrenal metastasis. The incidence of contralateral adrenal metastases are rare, they, however, can occur before, simultaneously or even after the primary neoplasm manifests clinically. Only a few synchronous and metachronous contra lateral adrenal metastases have been reported. We report a case of renal cell carcinoma with synchronous contralateral adrenal and lung metastasis.

Clinical and pathological characteristics and prognostic evaluation of high-risk small renal carcinoma

Objective To study clinical and histopathological features of high-risk small renal carcinoma and provide theoretical basis for the individualized treatment. Methods This retrospective study analyzed the clinical and histological data of 21 patients of high-risk small renal cell carcinomas which were highly aggressive or advanced stage, admitted from Jan 2000 to July 2015. There were 15 males and 6 females, and the average age was (61.5±7.1) years (ranged 27 to 75 years). The mean diameter of tumors was 3.3cm (ranged 2.0 to 4cm). The study mainly focused on pathological character and stage, Fuhrman grading, existence of perirenal tissue or vascular invasion, venous embolus and distant metastasis. Results Of all these 21 cases, 17 cases were clear cell carcinomas, 1 was papillary carcinoma, 2 were hybrid cellular tumor (malignant rhabdoid tumor and sarcomatoid carcinoma) and 1 was sarcomatoid carcinoma. Among the 17 clear cell carcinoma cases, 12 were Fuhrman grade Ⅱ, 5 were grade Ⅲ and one was grade Ⅳ. Tumor infiltrated renal vein or its branches and renal vein embolus were found in 7 cases. The tumor infiltrated perirenal or renal sinus fat were found in 11 cases. Synchronous lung and local lymph nodes metastasis were found in 3 patients respectively. Moreover, there was 1 case with metastasis to the brain (Fuhrman Ⅳ). The final clinical stage were T3aN0M0 in 14, T1aN1M0 in 3 and T1aN0M1 in 4 cases. Conclusions Small renal tumors are heterogeneous in its biological behavior and the minorities are aggressive with infringement of perirenal fat or simultaneous local lymph node or distant metastasis. When the tumor is greater than 3.0 cm in diameter and with high grade in Fuhrman classification, sarcomatoid carcinoma are more likely to be highly aggressive and advanced stage. Key words: Kidney neoplasms; Pathology; Neoplasm metastasis

Colorectal cancer with synchronous lung metastases: clinical characteristics, treatment, prognosis

Objective: to evaluate the impact of cytoreductive surgery on treatment results in patients with colorectal cancer and synchronous lung metastases. Materials and methods. This retrospective investigation analyzed the results of therapy in patients with colorectal cancer and synchronous lung metastases who had been treated in the period 2000 to 2012. The investigators studied the following indicators: the impact of cytoreductive surgery on the survival of patients with this condition, the clinical characteristics of a group of patients with isolated lung involvement, the dissimilarity of this group from a group of patients with extrapulmonary metastases, the possibility of performing complete cytoreductive surgery in patients with varying degrees of a metastatic process, and the number of patients with complications in primary tumor. Results. The investigations included the data of 112 patients with colorectal cancer and synchronous lung metastases. Out of them, 38 (33.9 %) patients had isolated lung involvement and the latter was associated with extrapulmonary metastases in 74 (64.1 %). In 16 of the 38 patients, isolated lung metastases were regarded as resectable and complete cytoreductive surgeries were performed. The median follow-up in the examined group was 15.2 months. One- and two-year overall survival rates were 63 and 45 %, respectively. The patients with isolated lung metastases were observed to have higher 2-year overall survival rates than those with multiple metastases (63.0 and 37.5 %, respectively; p = 0.055) and there were significantly higher 2-year overall survival rates in patients after removal of primary tumors than in those who had not undergone cytoreductive surgery (21.0 and 52.5 %, respectively; p = 0.004). Two-year overall survival rates were 72.5 % in the complete cytoreductive treatment group. Conclusion. The prognosis in the patients with colorectal cancer and synchronous lung metastases was better than that in those with isolated lung involvement and in those whose primary tumor had been removed. Complete cytoreductive surgical treatment can provide long-term survival in this category of patients.

Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer.

Backgrounds/AimsAggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal.MethodsClinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed.ResultsOf the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively).ConclusionsSurgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.

Predictors and outcome of complete removal of colorectal cancer with synchronous lung metastases.

The prognosis-improving effect of radical surgery has been demonstrated in patients with colorectal cancer (CRC) with liver metastases. However, few studies have examined the effectiveness of treatments for CRC with metastases in organs other than the liver. The aim of the present study was to evaluate the outcome of surgical treatment for CRC with lung metastases. The study retrospectively examined 57 primary CRC patients (28 men, median age of 65 years) with synchronous lung metastases who underwent surgery between 2003 and 2012. Data such as clinicopathological parameters, metastasized organs, and the details of surgery, recurrence and survival periods were extracted and analyzed. Curative resection was performed in 10 patients ('curative group'). Primary tumors were resected without metastasectomy in 37 patients ('non-curative group'), whereas 10 underwent stoma surgery ('stoma group'). All the metastasized lesions were confined to the lung and liver in the curative group. By contrast, 43% of the non-curative/stoma groups had metastases in organs other than the lung and liver. Multivariate analyses indicated the absence of extrahepatic metastases as the only predictor of curative resection in CRC patients with lung metastases. The 3-year overall survival rates for the curative, non-curative and stoma groups were estimated as 74, 20 and 17%, respectively (P=0.0007). In conclusion, curative resection was possible in CRC patients with lung metastases if other disseminated lesions were limited to the liver and this treatment resulted in a longer survival time. Furthermore, palliative resection may contribute to a better prognosis compared to stoma surgery alone in selected cases.

Pathological characteristics of small renal carcinoma and its clinical value

Objective To study the clinical and histopathologic features of small renal carcinoma (diameter≤4 cm)and provide theoretical basis for evaluating the safety, efficacy and prognosis of nephron sparing surgery. Methods This retrospective study collected the pathological data of 490 patients with small renal cell carcinoma, who were treated in our hospital, from May 2000 to October 2014. We recorded and analyzed the tumor size, histological subtype, Fuhrman grading, pathological stage, the existence of mulifocality, vascular invasion, tumor psuedocapsule, hemorrhage or necrosis and distant metastasis. Results The median diameter of tumor was (3.2±0.6)cm, ranged 0.6 to 4.0 cm. Of all the subjects, 422 (86.1%) were clear cell carcinoma, 32 (6.5%) were chromophobe cell carcinoma, 23(4.7%)were papillary carcinoma and 13(2.7%)were other rare types. Among the 422 clear cell carcinoma cases, 27 were Fuhrman grade Ⅰ, 157 were Ⅰ-Ⅱ grade, 210 were grade Ⅱ, 21 were Ⅱ-Ⅲ grade, 7 were grade Ⅲ and no one was grade Ⅳ. Multifocal tumors were found in 18 cases (3.7%) and tumor embolus of renal vein was found in 6 cases (1.2%). Intact psuedocapsule were found in 326 (66.5%) tumors with the thickness ranged from 0.2 to 1.0 mm. Tumor infiltration without the psuedocapsule penetration were found in 82 cases (16.7%), penetrated into the psuedocapsule were found in 11 cases (2.2%), infringement of perirenal fat were found in 9 cases (1.8%). Hemorrhage and necrosis were found in 240 cases (48.9%), synchronous lung metastases occurred in 3 patients (0.6%). Logistic regression analysis revealed that tumor invasion and pseudocapsule penetration were related to Fuhrman Ⅱ-Ⅲ, Ⅲ and tumor diameter (P=0.04). Moreover, tumor size was related with histological grade and renal capsule invasion (P=0.02). Nevertheless, there was no relationship among tumor size, renal vein embolus or mulifocality(P=0.35). Conclusions Although most small renal tumors are high differentiation and low grade, but rare cases are aggressive with infringement of perirenal fat or early distant metastasis, suggesting heterogeneity in its biological behavior. Most small renal tumors have obvious psuedocapsule. When the tumor size is greater than 3.0 cm and its Fuhrman classification was high, the psuedocapsule and perirenal fat are more likely to be infiltrated. Nephron sparing surgery should remove the tumor and its surface adipose tissue entirely. Key words: Renal cell carcinoma; Pathology; Neoplasm metastasis; Mulifocality; Nephron sparing surgery

154P - Surgical Treatment of Synchronous Lung Metastasis in Patient with Osteosarcomas and Soft Tissue Sarcomas

154P - Surgical Treatment of Synchronous Lung Metastasis in Patient with Osteosarcomas and Soft Tissue Sarcomas

Unusual synchronous skeletal muscle and lung metastasis in papillary thyroid cancer: A case report and review of the literature.

Papillary thyroid cancer (PTC) frequently metastasizes to the cervical lymph region and less often to the lung and bone. Metastasis to the skeletal muscles from PTC is extremely rare, especially concurrent lung and skeletal muscle metastases. The present study reports the case of a 31-year-old man with synchronous metastasis to the skeletal muscle and lung from PTC, six years following total thyroidectomy and consecutive 131Iodine treatments. Magnetic resonance imaging (MRI) revealed a 1.7×1.2×1.5 cm mass in the left gastrocnemius muscle, indicating a neurogenic tumor. The mass was subsequently resected and confirmed via histopathology to be metastatic PTC. We propose that, in the follow-up of patients with PTC, the measurable serum thyroglobulin level, whole body scan and other imaging modalities including MRI or positron emission tomography/computed tomography, must be closely monitored for potential distant metastases, particularly in cases of PTC with aggressive pathological behavior.

297. Multimodal approach to stage IV rectal cancer treatment

297. Multimodal approach to stage IV rectal cancer treatment

298. Cytoreductive surgery in colorectal cancer patients with synchronous lung metastases

298. Cytoreductive surgery in colorectal cancer patients with synchronous lung metastases

A case report on efficacy of Abound™ for anti-EGFR antibody-associated skin disorder in metastatic colon cancer

BackgroundPanitumumab is a full human epidermal growth factor receptor (EGFR) monoclonal antibody, an agent for metastatic colorectal cancer therapy. One of the most general adverse events of anti-EGFR monoclonal antibody therapy is skin disorder. At the present time, although prophylaxis of skin disorder is important for continuation of cancer therapy, there are no effective precautionary treatments.Case presentationA 73-year-old male with sigmoid colon cancer and synchronous lung metastasis was treated with panitumumab, an alone anti-EGFR monoclonal antibody as the third-line therapy.During the nine courses of the therapy, the response was stable disease (SD), but skin disorder gradually appeared obviously (CTCAE version 4.0: Grade 2). After 1 month of administration of Abound™, symptoms of the skin disorder improved (CTCAE version 4.0: Grade 1), thus the antibody therapy could be continued.ConclusionWe report that Abound™ was apparently effective in the treatment for anti-EGFR antibody-associated skin disorder. In the future, Abound™ could be expected as an agent for skin disorder as one of the side effects of colorectal cancer therapy.

肺転移巣と原発巣を外科的切除した肝内胆管癌の1例

肝内胆管癌の単発肺転移はまれである．今回肝内胆管癌，十二指腸乳頭部癌および肝内胆管癌の肺転移を二期的に切除した症例を経験したので報告する．症例は81歳，男性．整形外科通院中に胸部単純X線検査にて左中肺野の結節影を指摘され，精査の結果，肺癌，肝内胆管癌および十二指腸乳頭部癌の三重癌と術前診断された．二期的切除の方針にて，肝左葉切除術，左尾状葉切除術および幽門輪温存膵頭十二指腸切除術をまず先行させ，その術後37日目に左上葉切除術が施行され合併症なく退院した．病理組織検査にて肝内胆管癌肺転移と診断された．腫瘍は術後11ヵ月で肺に再発し，その11ヵ月後に患者は癌死した．医学中央雑誌で検索する限り本邦において肝内胆管癌の肺転移切除報告は自験例を除き1例のみである．他の文献と合わせ，肝内胆管癌の肺転移に対する外科的治療の意義を考察する．

An autopsy study of synchronous intratesticular and mediastinal sarcoma with pulmonary metastasis

Most testicular sarcomas arise from germ cell tumors (GCTs) viz. teratoma or spermatocytic seminoma. Pure intratesticular sarcomas are very rare. We present an autopsy report of non-germ cell primary intratesticular sarcoma with synchronous mediastinal sarcoma and lung metastasis in a young male who presented with symptoms of mediastinal compression and simultaneously had a significant gradually enlarging testicular mass.

Alveolar soft part sarcoma—radiologic patterns in children and adolescents

Alveolar soft part sarcoma is a rare but highly malignant tumour and little is known about its radiologic pattern in children. To describe the radiologic features of alveolar soft part sarcoma in children and adolescents. We retrospectively analysed the clinical and imaging data of six children age 7-17 years at diagnosis, with histologically or genetically proven alveolar soft part sarcoma. The tumours were located deep within muscles of the limbs (n = 4), in chest wall muscle (n = 1) and in the orbit (n = 1). High-flow feeding arteries, large drainage veins and intense enhancement were consistent findings by all imaging modalities. At MRI, all tumours demonstrated high signal intensity on T2-weighted images and high or iso-intense signal on T1-W imaging compared to muscle. In tumours larger than 70 mm in one dimension (n = 3/6), large vessels converging toward the tumour centre led to a highly vascularised central stellar area pattern. Five children demonstrated synchronous (n = 4/5) and metachronous (n = 1/5) lung metastases. Alveolar soft part sarcoma should be suggested when a highly vascularised, intramuscular mass demonstrating large feeding and drainage vessels converging toward a central stellar area is seen in children, especially if synchronous lung metastases are present.

Abstract 4755: Combination of PV-10 immuno-chemoablation and systemic anti-CTLA-4 antibody therapy in murine models of melanoma.

Abstract Rose bengal disodium (PV-10) is an investigational small molecule ablative agent currently entering pivotal phase 3 clinical testing as a monotherapy for locoregional control of cutaneous metastatic melanoma. Upon intralesional (IL) administration, PV-10 localizes to the injected tumor tissues while clearing rapidly from healthy tissue. Tumor infiltration with PV-10 leads to rapid necrosis of the injected lesion, with complete resolution common within 2-8 weeks. In phase 2 testing in 80 patients with Stage IIIB-IV(M1c) melanoma, IL PV-10 elicited an objective response in injected tumors in 51% of patients (CR:25%, PR:26%) after 1-4 treatment cycles. In addition to this direct ablative effect on injected tumors, some patients achieved an objective response in their monitored untreated tumors (CR:26%, PR:7% in 42 subjects with monitored untreated lesions) in an apparent immune-mediated bystander response that highly correlated with successful ablation of their injected tumors. Treatment was generally well tolerated, with adverse events confined mainly to the injection site and no grade 4 or 5 adverse events associated with use of PV-10. Recent nonclinical testing in the B16-F10 murine melanoma tumor line has confirmed that PV-10 ablation induces tumor-specific immunity, resulting in marked suppression of synchronous lung metastases upon ablation of a flank tumor and tumor-specific IFN-γ production. In this study we assess potential benefit of combination of PV-10 immuno-chemoablation with the hamster anti-murine CTLA-4 antibody 9H10 in bilateral flank and lung metastasis models (B16-F10 melanoma in C57BL/6 mice). Results from these models will be reported and could support clinical development of combination therapy in advanced melanoma patients, such as stage IV patients with substantial tumor burden in locations inaccessible to PV-10 injection. The rapid reduction in tumor burden and tumor specific immunologic stimulation provided by PV-10 may complement the immune stimulation of anti-CTLA-4 antibodies such as ipilimumab without increased toxicity. Citation Format: Eric A. Wachter, Savannah Blair, Jamie Singer, Craig Dees. Combination of PV-10 immuno-chemoablation and systemic anti-CTLA-4 antibody therapy in murine models of melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4755. doi:10.1158/1538-7445.AM2013-4755

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma

BackgroundKRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes.MethodsCross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status.ResultsKRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients.ConclusionThe KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.