Metástasis cervical con primario desconocido, cambios en los paradigmas: revisión sobre el enfrentamiento clínico, estudio y tratamiento / Cervical metastases from unknown primary tumor, paradigm changes: review on clinical confrontation, study and treatment

Resumen En adultos, una masa cervical detectada mediante examen físico o un estudio de imagen puede ser la única manifestación de un cáncer proveniente de cabeza y cuello. Un retraso en el diagnóstico repercute en el pronóstico de la enfermedad, por lo que debe haber un alto índice de sospecha. Las metástasis cervicales con primario desconocido (MCCPD) son tumores metastásicos en los que el estudio diagnóstico no logró identificar el sitio primario del cáncer, con una histología predominantemente de tipo escamosa. Según algunos estudios, el origen más frecuente resultó ser la orofaringe, incluyendo amígdala palatina y base de lengua. Factores de riesgo conocidos son edades avanzadas, consumo de tabaco y de alcohol. Actualmente, la infección por el virus del papiloma humano (VPH) está teniendo un rol cada vez más importante como factor de riesgo, formando parte de entre 20%-25% de los cánceres de cabeza y cuello. Al enfrentarse a un paciente con masa cervical es importante realizar una completa anamnesis y examen físico acucioso para detectar cualquier elemento sugerente de malignidad. Se debe complementar con nasofibroscopía para visualizar estructuras que no alcanzan a evaluarse en el examen habitual. También se puede orientar la búsqueda del primario desconocido en base a los patrones de drenaje linfático. Dentro del estudio complementario se puede comenzar con una tomografía computada (TC) y se puede considerar también el ultrasonido o un PET/TC. Si con esto aún no se logra definir el primario, continuar con una punción aspirativa con aguja fina (PAAF), luego biopsia core que consiste en tomar una muestra del centro de la lesión guiada por ecografía, si fuese necesario, incluyendo inmunohistoquímica para VPH; ambos estudios histológicos son preferibles en vez de una biopsia abierta debido al menor riesgo de diseminación y complicaciones. El siguiente paso incluye estudio endoscópico y biopsias bajo anestesia. El tratamiento de los pacientes con MCCPD, va a depender de factores relacionados con el estadio de la enfermedad: desde cirugía o radioterapia (RT) únicas, cirugía más RT, y en algunos casos quimioterapia. Se recomienda seguimiento clínico frecuente durante los primeros años y con imágenes dentro de los 6 primeros meses postratamiento.

Abstract In adults, a cervical mass detected by physical examination or an imaging study may be the only manifestation of cancer from the head and neck. A delay in the diagnosis affects the prognosis of the disease, so there must be a high index of suspicion. Cervical metastases from unknown primary tumor (CUP) are metastatic tumors in which the diagnostic study failed to identify the primary site of cancer, with predominantly squamous histology. According to some studies, the most frequent origin was the oropharynx, including palatine tonsil and tongue base. Known risk factors are advanced ages, tobacco and alcohol consumption. Currently, human papilloma virus (HPV) infection is playing an increasingly important role as a risk factor, being the cause of between 20-25% of cancers of the head and neck. When confronting a patient with cervical mass it is important to carry out a complete anamnesis and a thorough physical examination to detect any element suggestive of malignancy. Physical examination could be complemented with a flexible nasal endoscopic to evaluate structures that can not be evaluated in the habitual examination. The search for the unknown primary can also be oriented based on lymphatic drainage patterns. Within the complementary evaluations, one can start with a study of images such as computed tomography (CT) or magnetic resonance imaging (MRI) with contrast, and also could consider ultrasound or PET/CT. If the primary can not be defined yet, fine needle aspiration (FNAP) can be the next choice and then a core biopsy that consisting of taking a sample from the center of the ultrasound-guided lesion, if necessary, including immunohistochemistry for HPV; both histological studies are preferable to an open biopsy because of the lower risk of complications. The next step searching for the primary includes endoscopic study and biopsies under anesthesia. Regarding to the management of patients with CUP, it will depend on factors related to the stage of the disease: from surgery or radiotherapy (RT) only, surgery and RT, and in some cases chemotherapy. Frequent clinical follow-up is recommended during the first years and images within the first 6 months after treatment.

Making surgery safer by centralization of care: impact of case load in penile cancer.

PURPOSE: Penile cancer is a rare but aggressive disease, often requiring a rapid and extensive surgical treatment of the primary tumor and staging or treatment of the inguinal lymph node basins. Current management and guidelines of the disease are mainly based on retrospective data, as there is a lack of controlled trials or large series. The purpose of this work is to review contemporary data on the impact of centralization and formation of rare disease networks on penile cancer care and outcomes. METHODS: This narrative, non-systematic review is based on publications retrieved by a PubMed and EMBASE search and on the current guidelines of the European Association of Urology, the National Institute for Health and Care Excellence, and the National Comprehensive Cancer network. RESULTS: The low case load, particularly in non-specialized centres, combined with limited evidence regularly results in a disparity between the treatment strategy and the guidelines. The suboptimal guideline adherence is specifically the case for organ-sparing surgery and surgical staging of the groin areas in selected cases. Treatment of the disease in high-volume referral centres has been shown to improve the use of organ-sparing surgery, the utilization of invasive lymph node staging in high-risk patients, and finally has resulted in increased survival rates. CONCLUSIONS: The management of penile cancer in disease networks and in countries where centralized healthcare is offered positively influences functional and oncological outcomes. We propose that governments and health care providers should be encouraged to centralize healthcare for rare tumors such as penile cancer.

Prognostic significance of pathological tumor response and residual nodal metastasis in patients with esophageal squamous cell carcinoma after neoadjuvant chemotherapy followed by surgery.

BACKGROUND: The present study investigated prognostic factors in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) among various clinicopathological features related to neoadjuvant chemotherapy (NAC) and surgery, and the indications for additional treatment after surgery were considered. METHODS: A total of 113 patients with clinical stage II or III ESCC, who had undergone NAC followed by a thoracic esophagectomy with a three-field lymphadenectomy were retrospectively reviewed. NAC consisted of either two courses of cisplatin and 5-fluorouracil or three courses of docetaxel, cisplatin and 5-fluorouracil, with a new course beginning every 3 weeks. RESULTS: The overall survival (OS) rate was poorer in the pN-positive group than in the pN-negative group (P < 0.001). In terms of the histological therapeutic effect, the OS rate was poorer in the worse pathological responder group than in the better pathological responder group (P = 0.001). A multivariate analysis examining overall survival suggested that only pN (HR 3.204, P = 0.007) and worse pathological responder (HR 2.347, P = 0.041) were independent prognostic factors. The OS rate was compared among four groups classified according to the different combinations of pN and pathological response. A group of patients with pN-positive and worse pathological response had a significantly poorer outcome than the other groups. CONCLUSIONS: The present study suggested that patients with resectable advanced ESCC undergoing NAC followed by surgery, who have both pN and worse pathological response, have a poor prognosis.

Uncommon Presentation of Metastatic Squamous Cell Carcinoma of the Skin and Treatment Challenges.

BACKGROUND Squamous cell carcinoma is one of the most common keratinocytic skin cancers, the other being basal cell carcinoma. It is the second most common skin cancer after melanoma. Cutaneous squamous cell carcinoma is mostly a localized disease. The metastatic presentation is rare even in the presence of invasive disease. The metastatic potential depends on the presence of high-risk features at the time of diagnosis. Lung, liver, and bone are the frequent sites of metastasis. Local and locoregional disease undergoes excision with or without adjuvant radiation. However, we lack proper treatment paradigms for this metastatic disease. CASE REPORT We are reporting a case of an elderly female with a history of high-risk localized cutaneous squamous cell carcinoma treated with complete local excision and radiation presenting 5 years later with extensive disease to the lung and liver, abdominal nodes, and spinal fracture. The patient was not a candidate for chemotherapy due to kidney failure. On the basis of ongoing separate trials on different immunotherapies, she was started on nivolumab. CONCLUSIONS Treating metastatic cutaneous squamous cell carcinoma is a challenge considering the absence of phase III trials due to the rarity of this disease. Historically, platinum with or without 5-FU (fluorouracil), bleomycin, doxorubicin, and retinoic acid were used with variable responses. Data on epidermal growth factor receptor (EGFR) inhibitors on EGFR expressing tumors are available. However, even with the most recent reports on immunotherapy in patients with high programmed death-1 expression or high mutation burden, it is difficult to achieve good response.

Clinical outcomes with therapies for previously treated recurrent/metastatic head-and-neck squamous cell carcinoma (R/M HNSCC): A systematic literature review.

OBJECTIVES: A wide range of objective response rates (ORRs: 0-53%) among available treatments in patients with R/M HNSCC with progression on or after platinum-based chemotherapy (PBT) renders treatment selection a challenge. This systematic literature review (SLR) was intended to aid clinical decision-making by classifying historical studies to accurately characterize the response in second-line (progression on/after platinum-based therapy), and third-line (progression on/after platinum and cetuximab/other drug) settings. METHODS: SLR was performed to characterize the ORR, duration of response (DOR), progression-free survival (PFS) and overall survival (OS) with therapies recommended by the National Comprehensive Cancer Network (NCCN) guidelines. Clinical trials published in English between January 1, 1985, and September 30, 2016 were identified by searching the PubMed (Medline), Cochrane, and Embase databases. RESULTS: The SLR identified 34 key studies in second-line R/M HNSCC patients, and one of these included a third-line patient cohort. However, several studies did not enrol a strictly second-line population. Response in a true second-line setting was elucidated by categorizing the studies using a novel framework defined according to the extent to which enrolled patients were second-line. Only seven studies were strictly second-line, with an estimated pooled ORR of 4% (95% CI = 2-8%; N = 414) for methotrexate and 11% (95% CI = 7-15%; N = 235) for cetuximab, and a reported ORR of 14% (N = 78) from a single study of paclitaxel. The median DOR was limited with cetuximab (∼4 months) and paclitaxel (∼7 months), and not reported for methotrexate. Median PFS or time to progression (TTP) ranged from 1.7 to 3.5 months, and median OS from 4.3 to 6.7 months. The ORR in the only third-line study was 0% (95% CI = 0-7; N = 53) for the platinum + cetuximab combination. CONCLUSION: These findings emphasize the historically bleak prognoses in patients with R/M HNSCC following PBT progression. Anti-PD-1 therapies, namely pembrolizumab and nivolumab, represent novel treatment options that may improve clinical outcomes.

Site of Metastases as Prognostic Factors in Unselected Population of Stage IV Non-Small Cell Lung Cancer

Background: Advanced stage non-small cell lung cancer (NSCLC) is a heterogenous disease, yet, with the exception of targeted therapies, most guidelines recommended uniform treatment irrespective of tumor burden or sites of metastases and this may explain, in part, the wide range of responses to same lines of therapy. Aim of work: In this work we tried to explore the effect of metastatic sites in on overall survival (OS), in an unselected group of Non-small cell lung cancer patients who received different treatments line. Methods: A retrospective analysis was performed on patients with stage IV NSCLC who received systemic treatment at UAB Cancer Center (NCI designated comprehensive cancer center) between 2002 to 2012. The details of sites of metastases, systemic therapy and overall survival were recorded for each patient. Result: In 409 patients who received systemic treatment, there was statistically significant lower OS in those presenting with liver metastases (p<0.001), adrenal metastases (p=0.011) and metastases to abdominal lymph nodes (p=0.014). There was no statistically significance difference in OS in patient presenting with pleural metastases or effusion (p=0.908), metastases to heart or pericardium (p=0.654), metastases to bone (p=0.281), brain (p=0.717) or skin and subcutaneous tissue (p=0.642). Conclusion: Intra-abdominal metastases confer a particularly poor prognosis in stage IV NSCLC treated with systemic therapy and may identify patients in whom aggressive treatment beyond first line therapy is not appropriate.

Clinical Application of Genomic Profiling With Circulating Tumor DNA for Management of Advanced Non-Small-cell Lung Cancer in Asia.

BACKGROUND: Genomic profiling of cell-free circulating tumor DNA (ctDNA) is a potential alternative to repeat invasive biopsy in patients with advanced cancer. We report the first real-world cohort of comprehensive genomic assessments of patients with non-small-cell lung cancer (NSCLC) in a Chinese population. PATIENTS AND METHODS: We performed a retrospective analysis of patients with advanced or metastatic NSCLC whose physician requested ctDNA-based genomic profiling using the Guardant360 platform from January 2016 to June 2017. Guardant360 includes all 4 major types of genomic alterations (point mutations, insertion-deletion alterations, fusions, and amplifications) in 73 genes. RESULTS: Genomic profiling was performed in 76 patients from Hong Kong during the 18-month study period (median age, 59.5 years; 41 men and 35 women). The histologic types included adenocarcinoma (n = 10), NSCLC, not otherwise specified (n = 58), and squamous cell carcinoma (n = 8). In the adenocarcinoma and NSCLC, not otherwise specified, combined group, 62 of the 68 patients (91%) had variants identified (range, 1-12; median, 3), of whom, 26 (42%) had ≥ 1 of the 7 National Comprehensive Cancer Network-recommended lung adenocarcinoma genomic targets. Concurrent detection of driver and resistance mutations were identified in 6 of 13 patients with EGFR driver mutations and in 3 of 5 patients with EML4-ALK fusions. All 8 patients with squamous cell carcinoma had multiple variants identified (range, 1-20; median, 6), including FGFR1 amplification and ERBB2 (HER2) amplification. PIK3CA amplification occurred in combination with either FGFR1 or ERBB2 (HER2) amplification or alone. CONCLUSION: Genomic profiling using ctDNA analysis detected alterations in most patients with advanced-stage NSCLC, with targetable aberrations and resistance mechanisms identified. This approach has demonstrated its feasibility in Asia.

Guidelines of care for the management of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human cancer and has an increasing annual incidence. Although most cSCC is cured with office-based therapy, advanced cSCC poses a significant risk for morbidity, impact on quality of life, and death. This document provides evidence-based recommendations for the management of patients with cSCC. Topics addressed include biopsy techniques and histopathologic assessment, tumor staging, surgical and nonsurgical management, follow-up and prevention of recurrence, and management of advanced disease. The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cSCC is noted, as is general information on the management of patients with metastatic disease.

Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors.

While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated surgically, the additional work-up and treatments indicated for high-risk cSCC remain undefined. In recent years, improvements in tumor staging systems have allowed for the more accurate stratification of tumors into high- and low-risk categories. This insight, along with the publication of cSCC guidelines, brings us closer to the development of a consensus approach. The second article in this continuing medical education series addresses in question and answer format the most common questions related to advanced and high-stage cSCCs, with a simplified flowchart. The questions include the following: 1) Does my patient have high-risk cSCC?; 2) What is the next step for patients with cSCC and palpable lymphadenopathy?; 3) In patients with no clinically evident lymphadenopathy, who are candidates for lymph node staging?; 4) What forms of radiologic imaging can help detect subclinical lymph node metastases?; 5) What is the role of sentinel lymph node biopsy in cSCC?; 6) Which patients with cSCC need adjuvant radiation therapy?; 7) Is adjuvant chemotherapy an option for patients with high-stage cSCC after surgery?; 8) Are targeted and immunologic therapies an option for advanced cSCC?; 9) How often should I follow up with my patient after he/she has been diagnosed with a high-risk cSCC?; 10) What are the options for chemoprophylaxis in a patient with an increased risk of cSCC?; and 11) What chemopreventive measures can be started in coordination with medical oncology or transplant physicians?

C-reactive protein to albumin ratio is a prognostic factor for patients with cStage II/III esophageal squamous cell cancer.

C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.

Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma.

Neoadjuvant treatment has become standard care for patients with resectable esophageal cancer. However, some patients cannot undergo surgery or curative resection because of disease progression during neoadjuvant treatment. The aim of this study is to identify the pretreatment characteristics of patients in whom neoadjuvant treatment failed. The study enrolled 231 patients who underwent chemotherapy with cisplatin and 5-fluorouracil (CF) as neoadjuvant therapy for T1N1-3 or T2-3 any-N esophageal squamous cell carcinoma (ESCC). Of these patients, 201 (87.0%) underwent curative resection (R0) and 30 (13.0%) could not undergo curative resection; 19 patients (8.2%) underwent incomplete resection (R1 or R2), and 11 patients (4.8%) could not undergo surgery because of disease progression. We compared clinical characteristics and survival between patients who underwent curative resection (curative group) and those who could not undergo curative resection (noncurative group) to determine the factors predicting noncurative treatment. The noncurative group had significantly worse disease-specific survival than the curative group (P < 0.001). All patients in the noncurative group had cT3 tumors. In 141 patients with cT3 tumors, those in the noncurative group were more likely to have higher serum SCC antigen concentration (P = 0.021), location of the main tumor in the upper to the middle third of the esophagus (P = 0.071), intramural metastases (P < 0.001), advanced N category (P = 0.016), and bulky lymph node metastases (P = 0.060). Multivariate logistic regression analysis identified location of the main tumor in the upper to the middle third of the esophagus (P = 0.047), intramural metastases (P = 0.002), and nodal metastases (N1, P = 0.014; N2, P = 0.015, respectively) as independent predictors of treatment failure in patients with cT3 tumors. Neoadjuvant CF therapy alone may not be effective for patients with cT3 tumors accompanied by these risk factors, and the efficacy of alternative strategies, such as triplet chemotherapy or chemoradiotherapy, should be evaluated.

Double-blind, randomized phase 3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer: Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group (C0590).

BACKGROUND: 13-Cis retinoic acid (13-CRA) is a synthetic vitamin A derivative. High-dose 13-CRA in patients with squamous cell cancers of the head and neck (SCCHNs) reduces the incidence of second primary tumors (SPTs). The authors report long-term results from a phase 3 randomized trial that compared treatment with low-dose 13-CRA versus placebo for patients who had early stage SCCHN, with a focus on the development of SPTs and overall survival (OS). METHODS: In total, 176 patients who received treatment for stage I/II SCCHN were randomized to receive either low-dose 13-CRA (weight-based dose of 7.5 mg or 10 mg) or placebo for 2 years. A competing-risk approach and the log-rank test were used to compare the time to SPT and OS, respectively, between groups. RESULTS: 13-CRA neither significantly reduced the cumulative incidence of SPT (P = .61) nor improved the time to SPT (hazard ratio [HR] for 13-CRA/placebo; 0.86; P = .61). Despite limited power, there was a trend toward improved OS for the 13-CRA arm (HR, 0.75; P = .14), particularly among patients whose index tumor was surgically excised (N = 26; HR, 0.50; P = .057) and among women (N = 39; HR, 0.44; P = .065) and never/former smokers (N = 129; HR, 0.61; P = .055), with a median follow-up of 16 years. The main 13-CRA related toxicities were dry skin and cheilitis. CONCLUSIONS: Treatment with low-dose 13-CRA for 2 years did not decrease the incidence of SPT; subset analysis indicates a potential survival advantage among patients who are women and never/former smokers. More targeted interventions based on clinical risk factors and molecular characterization of tumors may yield greater success in future prevention trials. Cancer 2017;123:4653-4662. © 2017 American Cancer Society.

Refining the Role of Lymph Node Biopsy in Survival for Patients with Nasopharyngeal Carcinoma: Population-Based Study from the Surveillance Epidemiology and End-Results Registry.

BACKGROUND: The updated version of the National Comprehensive Cancer Network (NCCN) guidelines revised pretreatment workup for nasopharyngeal carcinoma (NPC) into "biopsy of the primary site or neck." Despite provision of important diagnostic information, concerns regarding tumor cell dissemination limit the application of lymph node biopsy. This study aimed to investigate whether biopsy of the neck is associated with impaired survival in NPC. METHODS: A propensity score-matched, population-based cohort identified from the Surveillance, Epidemiology, and End Results database was used to compare overall survival (OS) and disease-specific survival (DSS) of patients who underwent pretreatment cervical lymph node biopsy without subsequent neck dissection or removal of node compared with patients who did not undergo node biopsy. RESULTS: Of 2910 eligible patients, 416 (14.3%) underwent pretreatment lymph node biopsy. After use of control for patient, tumor, and demographic characteristics, biopsy was not associated with impaired OS (hazard ratio [HR], 1.15; 95% confidence interval [CI] 0.89-1.47; P = 0.29) or DSS (HR, 1.07; 95% CI 0.81-1.40; P = 0.63). Interestingly, in the subgroup analysis, the unfavorable effect of biopsy was observed for patients with differentiated non-keratinizing squamous cell carcinoma (but not other histologic types). Race did not positively alter the survival outcomes. CONCLUSIONS: The findings provide reference for clinical practice, showing that pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, except for patients with differentiated non-keratinizing squamous cell carcinoma. The recommended NCCN guidelines would be more specific by adding details to the general recommendation that neck biopsy is safe for all patients. Future prospective studies are needed to verify the study findings.

Neoadjuvant versus adjuvant chemoradiation for stage II-III esophageal squamous cell carcinoma: a single institution experience.

Esophageal cancer is the eighth most common cancer worldwide. It is the fourth most common cause of cancer death in China and esophageal squamous cell carcinoma (ESCC) is the most prevalent histologic type. Many clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation therapy in potentially resectable ESCC; however, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with resectable stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. A review of stage II/III thoracic ESCC patients who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation was performed. Chemotherapy regimen consisted of cisplatin 75 mg/m2 divided into 3 days and fluorouracil 500 mg/m2 on days 1 to 5. The patients who underwent neoadjuvant therapy were treated with one cycle of chemotherapy concurrently with radiotherapy (40 Gy in 20 fractions, 5 days/week), and those receiving adjuvant therapy were treated with two cycles of chemotherapy concurrently with radiotherapy (46-50 Gy in 23-25 fractions, 5 days/week). A total of 122 patients met inclusion criteria, of which 49 underwent neoadjuvant chemoradiation and 73 underwent adjuvant chemoradiation. Median follow up was 36.5 months. The median survival times and 3, 5-year overall survival (OS) rates for the neoadjuvant and adjuvant groups were 39.3 versus 31.5 months, and 53.0%, 45.7% versus 42.9%, 29.7%, respectively (P = 0.091). For the patients with stage III ESCC, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 39.3 versus 21.3 months, and 43.4% versus 21.0%, respectively (P = 0.021). Among lymph node-positive patients, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 55.6 versus 23.7 months, and 43.0% versus 25.7%, respectively (P = 0.085). The incidence of perioperative and postoperative complications was comparable between the two groups (P > 0.05). For patients with resectable stage II/III ESCC, neoadjuvant chemoradiation does not increase postoperative complications and is associated with a trend toward better OS when compared to adjuvant chemoradiation.

Isolated local recurrence or solitary solid organ metastasis after esophagectomy for cancer is not the end of the road.

Recurrent disease after esophagectomy bears an infaust prognosis, especially when multiple recurrences are present. But little is known about survival in patients with limited recurrence (solitary locoregional recurrence or solid organ metastasis). Herein, we report our experience with these subgroups. We analyzed 1754 consecutive patients surgically treated with curative resection for esophageal cancer and cancer of the gastroesophageal junction between 1990 and 2012. Seven subgroups were defined according to the recurrence type (locoregional vs. organ metastasis), the site of recurrence (abdominal, thoracic, cervical for lymph nodes and lung, liver, adrenals and others for organ metastasis) and also the number of lesions (one vs. multiple lymph node stations or organ metastasis) Of these groups; clinical isolated locoregional recurrence (ciLR) was defined as solitary lymph-node recurrence confined to one compartment (cervical, thoracic or abdominal, within or outside surgical dissection-field) at clinical staging. Clinical solitary solid organ metastasis (csSOM) was defined as metastasis in a resectable solid organ, i.e. liver, lung, brain or adrenal. Salvage therapies were grouped in five categories. Kaplan-Meier curves were used to calculate survival. Recurrent disease was observed in 766 patients (43.7%) with overall 5-year survival of 4.5% after diagnosis of recurrence. Fifty-seven patients (7.4%) showed ciLR and 110 (14.4%) csSOM. Median time-to-recurrence was 16.8 months in ciLR and 9.9 months in csSOM (P = 0.0074). Survival is significantly improved compared to supportive therapy when local therapy is possible (P < 0.0001). In 25 (15%) of ciLR or csSOM patients, surgical therapy with or without systemic therapy, yielded a 5-year survival of 49.9% (median 54.8 months) after diagnosis of recurrence. When surgery was impossible or contraindicated, the combination of chemoradiotherapy appeared to be superior to chemotherapy alone (respectively 27.0% vs. 4.6% 5-year survival) or radiotherapy alone (no 5-year survival). Recurrent disease after esophagectomy is a common problem with poor overall survival. However prolonged survival could be obtained in selected patients if the recurrent disease is limited to ciLR or csSOM, if surgery (+/- systemic therapy) can be performed. If not a combination of chemoradiotherapy seems to offer the second best option. Patients presenting with a ciLR or csSOM should be discussed in a dedicated multidisciplinary team meeting as to evaluate and define the place of salvage treatment which in well selected cases could offer a perspective of prolonged survival.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Effects of Neoadjuvant Chemotherapy Plus Radical Surgery as Front Line Treatment Strategy in Patients Affected by FIGO Stage III Cervical Cancer.

BACKGROUND: To assess the clinical efficacy and prognostic outcome of neoadjuvant chemotherapy (NACT) plus radical surgery (RS) as front line treatment in patients with FIGO stage III cervical cancer (CC). METHODS: In this retrospective study, 52 FIGO stage III CC patients treated from 2005 to 2015 were included. All patients received platinum-based chemotherapy. Patients reporting clinical response or stable disease after NACT underwent to RS and bilateral systematic pelvic lymphadenectomy with or without aortic lymphadenectomy or anterior exenteration. Patients with progressive disease underwent palliative management. RESULTS: After NACT, clinical response was observed in 23 patients (44 %): 4 (7.7 %) complete and 19 (36.5 %) partial responses, respectively. Also, 15 patients (28.8 %) had stable disease and 14 (26.9 %) showed disease progression. RS was performed in 40 cases (76.9 %): respectively, 28 (70 %) and 7 (17.5 %) underwent type C2 and D radical hysterectomy, while 5 patients (12.5 %) underwent anterior exenteration. At pathological evaluation, 23 patients (57.5 %) had positive pelvic nodes and 4 (10 %) also had positive aortic nodes. In 6 patients (15 %), moderate-severe (G3-G5) complications occurred. A total of 27 patients (67.5 %) received adjuvant therapy: 16 patients (40 %) received chemotherapy, 10 (25 %) received chemoradiation and 1 (2.5 %) received radiotherapy. Disease relapse occurred in 24 cases (60 %). After follow-up period of 60 months, the median OS of the whole population included was 37 months. Among the 40 surgically treated patients, median OS and DFS were 48 and 23 months, respectively. CONCLUSIONS: NACT plus RS represent a valid alternative with acceptable morbidity for patients with stage III CC.

Differentiation of malignant cervical lymphadenopathy by dual-energy CT: a preliminary analysis.

The accurate diagnosis of malignant cervical lymphadenopathy remains challenging. In this study, we determined the value of quantitative parameters derived from dual-energy computed tomography (DECT) for differentiating malignant cervical lymphadenopathy caused by thyroid carcinoma (TC), salivary gland carcinoma (SC), squamous cell carcinoma (SCC) and lymphoma. We retrospectively analysed 92 patients with pathologically confirmed cervical lymphadenopathy due to TC, SC, SCC and lymphoma. All patients received a DECT scan before therapy. Using GSI (gemstone spectral imaging) Volume Viewer software, we analysed the enhanced monochromatic data, and the quantitative parameters we acquired included the iodine concentration (IC), water concentration (WC) and the slope of the spectral HU curve (λHU). One-way ANOVA showed significant differences in the IC and λHU among different groups (P < 0.05). Post-hoc pairwise comparisons demonstrated the IC and λHU of TC group were significantly higher than those of SC, SCC and lymphoma groups (P < 0.05). In addition, the IC and λHU of SC group were significantly higher than those of the SCC and lymphoma groups (P < 0.05). Other comparisons of IC and λHU values showed no significant differences (P > 0.05). The quantitative parameters derived from DECT were useful supplements to conventional computed tomography images and were helpful for distinguishing different malignant cervical lymphadenopathies.

ypN0: Does It Matter How You Get There? Nodal Downstaging in Esophageal Cancer.

BACKGROUND: ypN0 following induction treatment for advanced esophageal cancer improves survival. Importance of how ypN0 is achieved is unknown. This study evaluates survival in "natural" N0 (cN0/ypN0) and "downstaged" N0 (cN+/ypN0) patients. METHODS: Among patients treated with induction treatment and surgery, 83 CT scans were retrieved in digital format and re-evaluated by a radiologist, blinded to pathological nodal status: 28 natural N0, 37 downstaged N0, and 18 ypN+. Impact of N0 classification on survival and associations with survival were identified. RESULTS: Survival varied with ypN: 3-year survival was 84 % for natural N0 patients, 59 % for downstaged N0, and 20 % for ypN+ (p < .001). Compared with natural N0 patients, risk of cancer mortality was 3.8 for downstaged N0 and 7.6 for ypN+ (p = .01). Survival was also stratified by ypT: compared with ypT0 natural N0, who had the best survival, intermediate survival was seen in ypT+ natural N0 [hazard ratio (HR), 1.3] and ypT0 downstaged N0 (HR, 1.8), and poor survival in ypT+ downstaged N0 (HR, 9.5) and ypN+ (HR, 12.0) (p = .026). CONCLUSIONS: Natural N0 and downstaged N0 patients are different clinical entities: downstaging cN+ with induction treatment producing downstaged N0 improves survival only if there is concomitant primary cancer downstaging to ypT0. Intermediate survival is seen in downstaged N0 patients with complete tumor response. Natural N0 patients experience intermediate survival with incomplete response (ypT+). Complete response in natural N0 patients produces the best survival. Means of obtaining ypN0 status matters and requires a complete response for downstaged N0 patients to benefit from induction treatment.