Carcinoma of Unknown Primary Site: Outcomes in Patients with a Colorectal Molecular Profile Treated with Site Specific Chemotherapy

Purpose: Accurate identification of carcinoma of unknown primary site (CUP) patients with colorectal sites of origin may improve outcomes by directing colorectal chemotherapy rather than empiric chemotherapy. Clinical features, standard pathologic evaluation, treatment response, and survival of CUP patients whose tumors had colorectal genetic signatures were examined. Patients and Methods: We prospectively tested paraffin-embedded biopsies from 213 CUP patients using mRNA-based RT-PCR assays, and identified patients with colorectal genetic signatures. Results: Assays were successful in 185 specimens (87%);32 (17%) had colorectal genetic signatures. All 32 patients had carcinoma;colonoscopy was normal in 30 patients studied;29 patients (90%) had typical metastatic sites;17 (53%) had consistent IHC profiles (CK20+, CDX2+). Twenty-nine patients (90%) received first- and/or second-line colorectal chemotherapy regimens (response rates of 69% and 54%, respectively). Median, 2- and 4-year survivals for all 32 patients were 21 months, 42%, and 35%, respectively. Conclusion: The majority of CUP patients with colorectal molecular profile diagnoses responded to site-specific chemotherapy;median survival was similar to patients with known advanced colorectal carcinoma and superior to expected survival of CUP patients receiving empiric chemotherapy. Molecular profile assays can identify CUP patients with colorectal carcinoma;colorectal chemotherapy appears to improve outcomes.

Carcinoma of unknown primary and paraneoplastic dermatomyositis

Dermatomyositis is known to be associated with neoplastic disorders,however the presentation of carcinoma of unknown primary as dermatomyositis is rare. We describe a case index of 50-year-old female who presented with enlarged inguinal lymph nodes accompanied with symmetric proximal muscle weakness and erythematous plaques. Conventional basic work-up did not reveal the diagnosis,however,positron emission tomography-computed tomography and re-staining of the pathology specimen suggested the ovaries as the primary site. Chemotherapy including carboplatin paclitaxel and bevacizumab led to complete response of disease and improvement in the dermatomyositis. The present case emphasizes the importance of a thorough directed evaluation for the underlying cancer in patients with carcinoma of unknown primary presenting as dermatomyositis. We further provide an up-to-date detailed review of published data describing these clinical entities.

Surgical Treatment for Mediastinal Lymph Node Carcinoma of Unknown Primary

Carcinoma of unknown primary (CUP) is occasionally encountered in clinical oncology. Wide variation exists in CUP. We herein report a rare case of CUP of a mediastinal lymph node. A 61-year-old man with dermatomyositis was referred to our hospital for treatment of mediastinal adenopathy and gastric cancer. Biopsy of both lesions showed that they were histologically different from each other. Mediastinal lymphadenectomy and total gastrectomy were performed for a definitive diagnosis and radical cure. Pathological examination revealed two distinctly different disease processes. The patient underwent postoperative chemotherapy for residual gastric cancer. Twenty months postoperatively, he is alive with cancer. Although CUP usually has a poor prognosis, surgical treatment of metastatic mediastinal lymph node CUP is a feasible therapeutic option.

Analysis of Mortality Rates of the 5 Most Frequent Primary Cancer Sites in Brazil between 1979 and 2015 for Both Sexes

Introduction:Global estimates determined that there would be 14.1 million new cases of cancer and 8.2 million deaths from cancer.Objectives:To determine the adjusted mortality rates of the 5 most frequent primary sites of cancer and the mortality rates of the 5 most frequent primary in Brazil,between 1979 and 2015.Method:Epidemiological study between 1979 and 2015 based on data obtained from the Online Atlas of Mortality provided by the National Cancer Institute of Brazil(INCA)using information on cancer deaths obtained within the System of Information on Mortality(SIM)of Brazil Ministry of Health.Results:When analyzing the mortality rate of the 5 most frequent primary sites by type of cancer from 1979 to 2015 for both sexes,we show that in the year 2015 the cancers with the highest rates are:bronchi and lungs,breast,stomach,prostate and unknown primary location.A total of 527,980 deaths from bronchial and lung neoplasms were recorded,304,546 deaths from breast cancer were recorded,407,611 deaths from stomach cancer were recorded,268,061 deaths from prostate cancer were recorded,and 257,357 deaths due to neoplasia of unknown primary location were recorded.When we analyze the world standard rate and Brazil’s standard rate for mortality,we show that Brazil has higher values for the 5 most frequent primary sites by type of cancer.Conclusion:The epidemiological study of these values aims to determine what are the main descriptors and characteristics to determine preventive measures against the increase of this disease.

Primary ascending colon cancer accompanying skip metastases in left shoulder skin and left neck lymph node: A case report

BACKGROUND Lymph node skip metastases are common in lung,breast,and thyroid cancer patients,but are rare in colon cancer patients.Specifically,lymph node skip metastases occur in 1%-3%of colon cancer patients.Previous reports have demonstrated colon cancer skip metastases involving the retropancreatic and portocaval lymph nodes and Virchow's node;however,reports involving skip metastases into the left neck lymph nodes and left shoulder skin are extremely rare,as are related reports of clinical treatment and prognosis.CASE SUMMARY A 44-year-old Chinese man was admitted to the hospital for evaluation of persistent shoulder pain for 3 d and a cutaneous mass(3.0 cm×2.0 cm)on the left shoulder.The left shoulder cutaneous mass was excised and bisected,revealing tissues with a fish-like appearance.The pathologic diagnosis of the cutaneous mass suggested a signature[CDX-2(++),CK20(++),Ki-67(+)>50%]of infiltrating or metastatic colorectal adenocarcinoma.An enhanced computed tomography scan of the abdomen revealed chronic appendicitis with fecal stone formation,cecal edema,and a pelvic effusion.A colonoscopy revealed a cauliflower-like mass within the ascending colon area that involved the lumen.The surface of the ascending colon mass was eroded and bleeding;a biopsy was performed.The pathologic diagnosis of the colonoscopy biopsy was an ascending colon mucinous adenocarcinoma.The patient underwent a laparoscopic radical resection of the right colon based on the pathological diagnosis.The tumor was 5.0 cm×4.5 cm×1.8 cm in size and infiltrated the entire thickness of the intestinal wall with vascular tumor thrombi.No nerve tissue involvement was noted.The ileum and colon resection margins were negative.The postoperative pathologic analysis revealed non-metastatic involvement of ileocecal,pericolic,or peri-ileal lymph nodes.The postoperative medical examination revealed palpably enlarged lymph nodes in the left neck,and the following color Doppler ultrasound examination of the neck confirmed enlarged lymph nodes in the left neck.After surgical resection and pathologic diagnosis,a common pathologic signature consistent with resected cutaneous mass and right colon was identified,suggesting skip metastasis of left cervical lymph nodes.The patient was then treated with eight courses of chemotherapy and under followup evaluations for 4 years;currently,no tumor recurrences or metastases have been noted.CONCLUSION We report an abnormal skip metastasis involving the left shoulder skin and left neck lymph node in a patient with ascending colon adenocarcinoma.Specifically,we observed non-metastatic involvement of the lymph nodes around the tumor site but with metastases to the cervical lymph nodes.The standard surgical operations were performed to resect the cutaneous mass,tumor tissue,and cervical lymph nodes,followed by chemotherapy for eight courses.The patient is healthy with no tumor recurrences or metastases for 4 years.This clinical case will contribute to future research about the abnormal skip metastasis in colon cancers and a better clinical treatment design.

Long-term survivor of metastatic squamous-cell head and neck carcinoma with occult primary after cetuximab-based chemotherapy:A case report

BACKGROUND Cancer of unknown primary(CUP)is a histological proven malignant tumor whose origin cannot be detected despite careful examination.Most cervical lymph node metastases in CUP(80%)will originate from head and neck sites,and 15%show infiltration of squamous carcinoma cells.The survival rates of CUP are poor:The 5-year-survival rate ranges from 10%to 15%.First-line treatment recommendation for advanced,inoperable squamous cell carcinoma of head/neck(HNSCC)was cetuximab plus platinum-fluorouracil chemotherapy until recently,when checkpoint inhibitors proved clinically beneficial therapies.CASE SUMMARY Here,we report a case of a 42-year-old female patient with cervical and abdominal lymph node and distant bone metastases of an occult primary of the head and neck(squamous cell carcinoma,human papillomavirus positive).The cancer was diagnosed during pregnancy 10 years ago,and after giving birth,the patient was treated with cetuximab plus platinum-fluorouracil chemotherapy achieving complete remission(CR).CR lasted 26 mo when new metastases(abdominal lymph node,lumbar vertebral body)emerged.Both manifestations were irradiated.From then on,the patient has not received any further treatment,and her disease has remained controlled.Ten years after the initial cancer diagnosis,the patient is still alive and in good health,representing an exceptional case of HNSCC.CONCLUSION This case illustrates the exceptional clinical course and benefits of combined therapy approaches in advanced metastatic HNSCC with occult primary.

Array Comparative Genomic Hybridization as a Diagnostic Tool in Cancer

The knowledge of the primary origin of tumor is essential in designing an efficient cancer treatment algorithm. Useful diagnostic tools enable determination of primary origin of the tumor;however the majority of them require tissue examination. Recent years, exploration of circulating tumor cells enabled scientists to study different parameters using the painless liquid biopsy. The present study aimed to identify whether aCGH might be used as a diagnostic tool in cancer detecting the primary origin of the tumor. Blood was extracted from healthy individuals and cancer samples and CTCs isolated. DNA extracted from the above samples and aCGH experiments followed. The samples were blinded analyzed and then unmasked to calculate specificity and sensitivity of the method. The sensitivity was 94%, the specificity 88%, while the positive prediction rate of the primary tumor was 72%. aCGH is a powerful tool in cancer diagnosis and treatment plan with high sensitivity and specificity rates. It can be performed from blood sample, which makes it an appropriate method for every patient, mainly for patients with unknown origin of the primary tumor.

中国抗癌协会多原发和不明原发肿瘤诊治指南(2023年版)

原发灶不明肿瘤(cancer of unknown primary,CUP)和多原发肿瘤(cancer of multiple primaries,CMP),因其临床异质性高、发病率低、循证医学证据的相对匮乏及临床疾病认识的相对局限,目前诊疗仍面临巨大挑战。随着对疾病影像学、病理学、基因特点等认识的不断深入,多学科的协作和发展,以及分子靶向治疗和免疫治疗的针对性探索正在不断地更新对这部分患者治疗的理念和手段。本指南的制定旨在为临床工作者提供CUP和CMP患者诊疗的原则和纲要,为患者提供从诊断、治疗到康复的全流程规范化指导。

原发灶不明肿瘤诊疗进展与展望

原发灶不明肿瘤(cancer of unknown primary,CUP)是一种细胞异质性显著并且具有高度恶性表型的转移性疾病,并且很难通过常规的检查手段被检测出其原发灶。一些新的检测手段,如基因表达谱检测、肿瘤表观遗传学检测、液体活检等手段逐渐应用于CUP原发灶的确定上,基于此出现的器官特异性治疗、靶向治疗、免疫治疗等也均有较大的应用前景,其有望提高CUP患者诊断的精确性和特异性,延长患者生存时间,改善患者生存质量。本文针对CUP的前沿诊断技术和治疗选择及其进展进行综述。

原发灶不明肿瘤的诊断技术现状及进展

原发灶不明肿瘤(CUP)是一种经病理学检查确诊为转移性肿瘤,但目前通过详尽的临床信息和诊断手段仍无法明确其原发灶的一类异质性肿瘤。CUP的发病率约占所有肿瘤的1%~2%,其病程短、进展快,且患者的治疗和预后与原发部位有密切关系。明确原发灶是临床上诊断该疾病的难点,提高原发灶的检出率是CUP相关研究的重点。基因表达谱分析、高通量测序分析技术、表观遗传学以及液态活检等新技术相继被应用于CUP的原发灶的判断,具有较高的诊断准确率、敏感性和特异性。分子诊断指导下靶向治疗、免疫治疗及联合治疗等将开启CUP的精准治疗时代,CUP或可成为个体化治疗的典型代表。

二代测序技术在原发灶不明肿瘤诊疗中的研究进展

原发灶不明肿瘤(cancer of unknown primary,CUP)是一类罕见且预后不良的恶性肿瘤,分析和寻找原发灶、组织类型或分子免疫特征对改善患者的预后具有重要意义。在精准医疗背景下,二代测序(next-generation sequencing,NGS)可以利用肿瘤组织或外周血标本从基因层面对这类患者进行检测以指导诊断与治疗,延长患者生存期,改善预后。本文针对NGS样本的选择、NGS指导下的CUP患者的组织溯源、分子特征、指导治疗等方面进行综述。

2023年ESMO基于分子指导的原发灶不明肿瘤治疗新进展

原发灶不明肿瘤(cancer of unknown primary,CUP)是一类组织学上确定为转移并经过一系列检查仍未找到原发灶的肿瘤,占所有新发肿瘤的2%~5%。CUP具有侵袭性强、早期转移及预后差等特征。随着新兴基因检测和药物的应用,基因表达谱和基因组检测在揭示肿瘤分子特征中的价值日益凸显,基于分子指导的靶向治疗和免疫治疗等新的治疗选择也应运而生。本文就2023年欧洲肿瘤学会(European Society for Medical Oncology,ESMO)年会上报道的有关CUP的临床试验进行述评。

体外诊断技术在原发不明肿瘤诊断中的应用与展望

原发不明肿瘤(CUP)是一类经过全面检查仍未找到组织起源的转移性肿瘤。CUP具有强侵袭性,易发生早期转移和预后不佳等特点。随着体外诊断技术的发展,肿瘤组织起源基因检测可准确判断肿瘤的原发灶,有助于优化CUP患者的治疗方案和改善预后。本文就体外诊断技术在CUP诊断中的应用与展望进行综述。

不明原发灶颈部转移癌的诊断

虽然理论上所有的颈部转移癌都有原发灶的存在,但临床上并非所有的颈部转移癌都可以找到原发灶,原发灶的检出与否直接影响患者的生存率和生活质量。近年来,随着诊断仪器的开发、诊断技术的提高和诊断方法的改进,越来越多的不明原发灶颈部转移癌(unknownprimarycervicalmetastaticcarcinoma,UPCMC)被检测出原发灶。本文重点对UPCMC的定义、传统和新近发展的诊断方法进行综述。

原发灶不明颈淋巴结转移癌42例临床分析

目的 探讨原发灶不明颈淋巴结转移癌的诊断、治疗方法与预后的影响因素。方法 回顾分析我院 1992年 2月～ 1999年 2月收治的 4 2例原发灶不明颈淋巴结转移癌患者的临床资料。结果 全组的l、3、5年生存率分别为 71.4 % (30 / 4 2 ) ,4 5 .2 % (19/ 4 2 ) ,33.3% (14 / 4 2 )。随诊中有 14 .3% (6 / 4 2 )的原发灶不明颈淋巴结转移癌患者发现了原发灶。结论 影响原发灶不明颈淋巴结转移癌预后的主要因素是组织学类型 ,N分期 ,转移癌的部位 ,原发灶是否找到。对颈部转移性低分化癌、未分化癌或鳞癌应采用放射治疗 ,位于中上颈者应采用面颈联合野放射治疗 ,转移性腺癌应以手术治疗为主 ,晚期颈转移癌应采用化疗、放疗为主的综合治疗。

多西紫杉醇联合顺铂治疗原发灶不明癌的疗效观察

目的:分析多西紫杉醇联合顺铂治疗原发灶不明癌的疗效。方法:回顾性分析了2004年1月至2008年2月期间收治的15例原发灶不明癌患者,均未经过化疗,PS评分0-2,有可测量病灶,无器官功能障碍。方案:多西紫杉醇60mg/m2,d1;顺铂80mg/m2,d2,静脉化疗,每21天为一个周期,每2个周期后评价疗效。病情未出现进展者共完成4-6个周期。结果:15例患者中有1例因经济原因仅化疗1个周期,其余14例患者总有效率为50%,95%可信区间23%-77%,疾病控制率为78.6%,95%可信区间49%-98%;中位进展时间为5.5个月,中位生存时间为11.6个月;无化疗相关性死亡,常见的不良反应为白细胞减少(1-3级13人),恶心呕吐(1-2级11人),肾毒性(1-2级3人),外周神经毒性(1级3人),肝脏毒性(1-2级,3人),心脏毒性(1级1人)。结论:多西紫杉醇联合顺铂治疗原发灶不明转移癌安全有效,不良反应可以耐受。

长春瑞滨联合奈达铂治疗原发灶不明的颈淋巴结转移癌

目的:观察长春瑞滨联合奈达铂治疗原发灶不明的颈淋巴结转移癌的近期疗效和不良反应。方法:长春瑞滨25 mg/m2,加入生理盐水50 ml静脉滴注10 min,第1天和第8天;奈达铂80 mg/m2加入生理盐水500 ml中,静脉滴注2 h,第1天。21 d为1个周期。结果:治疗15例总有效率为66.7%,临床受益率为93.3%,主要不良反应为骨髓抑制,表现为白细胞及血小板减少,但在集落刺激因子支持下均可耐受,无治疗相关死亡。结论:长春瑞滨联合奈达铂治疗原发灶不明的颈淋巴结转移癌近期疗效较好,不良反应可以耐受。

多西他赛联合顺铂治疗原发灶不明转移癌临床观察

目的评价多西他赛联合顺铂治疗原发灶不明转移癌的疗效及毒副反应。方法回顾性分析2006年1月~2011年1月间我院化疗科收治的45例原发灶不明转移癌患者的临床资料。17例采用多西他赛联合顺铂方案：多西他赛60mg/m2,d1;顺铂25mg/m2,d1-3。每3周为1周期。治疗至疾病进展或出现不能耐受的毒性反应时停止。依据RECIST标准评价疗效,依据NCI CTC标准评价毒性,随访5年。其余28例采用其他方法治疗。比较两组在有效率、临床获益率和平均存活时间的差异。结果多西他赛/顺铂组17例共完成75个疗程化疗,平均每例患者完成4.41个疗程,CR 1例,PR 5例,SD 4例,有效率35.3%（95%CI 12.6%-58%）,临床获益率58.8%（95%CI 35.5%-82.1%）,平均无疾病生存期为9个月,平均存活时间为21.5个月。对照组28例,采用其他疗法,CR 1例,PR 4例,SD 5例,有效率17.9%（95%CI 3.7%-32.1%）,临床获益率35.7%（95%CI 17.9%-52.8%）,平均疾病进展期为5个月,平均存活时间为8.7个月。但两组有效率和临床获益率差异均无统计学意义（P〉0.05）。17例患者均可评价毒性,毒副反应主要为骨髓抑制、外周神经毒性和低钠血症。结论多西他赛/顺铂组治疗原发灶不明转移癌疗效较好,毒副反应可以耐受。

基因组时代下原发部位不明肿瘤诊治进展

原发部位不明肿瘤(cancer of unknown primary,CUP)是指组织学确认的转移性恶性肿瘤,而原发部位经详细检查后未能发现,占所有恶性肿瘤的3%~10%。CUP的诊断主要依靠影像学及组织病理学检测。基因组时代下,分子表达谱及表观基因组学方法协助鉴定肿瘤原发部位,准确率高,然而这些方法尚未在临床广泛开展。因此,推动其更方便地用于临床实践至关重要。CUP为一组异质性疾病,传统经验性治疗有效率低,而识别出15%~20%预后良好的亚型及采用器官特异性治疗能够提高患者生存。此外,基因组时代下,分子检测及二代测序技术的应用,为CUP中进行个体化靶向治疗提供了机会。近年来免疫治疗在肿瘤中取得突破性进展,本文对基因组时代下CUP诊治的挑战进行综述,期待靶向治疗和免疫治疗在CUP中有所突破。

一种新型肿瘤组织起源分子标志物的建立与评价

背景与目的：原发灶不明恶性肿瘤是一类转移性肿瘤的统称,在诊断时无法找到原发位点,约占所有恶性肿瘤的5%~10%。明确肿瘤的组织起源对于患者的诊断和治疗具有重要意义。方法：整合Array Express和Gene Expression Omnibus数据库中肿瘤类型明确的样本数据,构建涵盖22种常见肿瘤类型、5 800例样本的基因表达谱数据库;通过支持向量机递归特征消除算法筛选组织特异性基因,建立肿瘤分类模型;采用实时定量聚合酶链反应（real-time quantitative polymerase chain reaction,RTQ-PCR）检测石蜡包埋肿瘤组织中基因的表达水平,并将基因分型结果与病理诊断结果进行比较。结果：基于肿瘤基因表达谱大数据,筛选出96个组织特异性基因,其中包含常见的肿瘤相关基因,如钙黏蛋白1（cadherin 1,CDH1）、激肽释放酶相关酶3（kallikreinrelated peptidase 3,KLK3）和表皮生长因子受体（epidermal growth factor receptor,EGFR）等。在206例石蜡包埋组织样本中,182例的基因分型结果与病理诊断结果一致,准确率达到88.4%（95%CI：83.2%～92.4%）。结论：96基因RTQ-PCR检测对22种常见肿瘤类型具有较好的分类性能,可作为临床和病理诊断的辅助工具。