High-risk Squamous Cell Carcinoma Research Articles

Biópsia dinâmica do gânglio sentinelas no carcinoma espinocelular invasor do pénis: experiência de um serviço de uro‐oncologia em Portugal

ObjectivesThe 2014 European Association of Urology (EAU) guidelines on Penile cancer recommend dynamic sentinel node biopsy (DSNB) as a standard staging method for intermediate and high risk squamous cell carcinoma of the penis (SCCp), (≥ T1G2), c N0. The aim of this work is to evaluate the false negative rate and morbidity of our DSNB series. Material and methodsSince 2005 to 2014, 23 patients with SCCp and a patient with melanoma of the distal urethra, cN0, underwent DSNB in the urology department of Porto Portuguese Oncology Institute ‐ IPOPFG, EPE, Portugal. Bilateral inguinal ultrasound scan and fine needle aspiration cytology (FNAC) of suspicious inguinal nodes were not performed before DSNB.Lymphoscintigraphy starts in the morning of surgery with peri‐tumoral injection of albumin nanocoloid labeled with 99mTc. Peri‐operatively, patent blue is injected into the dermis in peri‐tumoral location. The sentinel node is identified during surgery with the aid of lymphoscintigraphy images, a portable probe which detects gamma rays and identification of the blue dye in lymph nodes and vessels. The false negative rate was calculated per patient.The complication rate was calculated per groin within 30 days of DSNB. ResultsIn 23 patients with SCCp, lymphoscintigraphy was bilateral in 7 patients. Biopsy was bilateral in 11 patients, with a mean number of lymph nodes excised per patient of 2; negative for metastasis in 20 patients. After median follow‐up of 45.5 months, we had a false negative. The false negative rate [1 false negative / (3 true positive + 1 false negative)] was 25%. The complication rate of BDGS per groin was 5.8%, with 2 minor linfoceles (Clavien I). ConclusionsInguinal ultrasound and FNAC of suspicious lymph nodes before DSNB, although operator‐dependent, seems very important to decrease our false negative rate. The referral of patients with SCCp for DSNB can increase the number of patients undergoing this nodal staging method in Portugal. The DSNB morbidity is minimal.

Surgical management of high-risk squamous cell carcinoma of the scalp: series of cases

Surgical management of high-risk squamous cell carcinoma of the scalp: series of cases

Concurrent cisplatin-based chemotherapy versus radiotherapy alone as adjuvant therapy for squamous cell carcinoma of the oral cavity bearing high-risk features

Background: To compare concurrent cisplatin-based chemoradiation in an adjuvant setting for high-risk squamous cell carcinoma of oral cavity terms of toxicity, local-regional control, and overall survival. Materials and Methods: A total of 54 patients of postoperative squamous cell carcinoma of oral cavity with high-risk features were randomized into two groups; postoperative radiation (60 Gy/30#/6 weeks) or postoperative concurrent chemoradiation (60 Gy/30#/6 weeks with weekly concurrent cisplatin 50 mg) arms. Results: Buccal mucosa was the most common sub site (44.4%) affected, followed by lower alveolus/alveolar ridge (37%) and most tumors (64.3%) were well-differentiated. About 67.3% of the patients completed their course of radiation within 6 weeks with only 69 patients receiving the scheduled 60 Gy of external beam radiation therapy dose. Only 6 patients out of 22 completed the 6 cycles of weekly chemotherapy with compliance decreasing most after 3 cycles. Mucositis and dysphagia were significantly higher in the chemoradiation arm. After a median follow-up of 47 months, the loco-regional control rate was 51.4% in the postoperative chemoradiation arm as compared to 35.56% in the postoperative radiation arm. The 5 years overall survival was 56.4% in postoperative chemoradiation arm as compared to 51.3% in the postoperative radiation only. Conclusion: Postoperative concurrent chemoradiation with weekly cisplatin in high-risk oral cancer gave an advantage in the loco-regional control rate and overall survival at the end of 47 months, with significant increase in acute toxicities Grade III and Grade IV toxicities.

Carcinoma espinocelular de la vulva: caso clínico

SUMMARY Background: Squamous cell carcinoma (SCC) is a malignant epithelial neoplasm. SCC can be divided into 4 groups: non-melanoma skin cancer (NMSC), head and neck, esophageal and lung cancer. The risk for metastasis of SCC is 0.3-3.7%. Vulvar SCC is approximately 3-5% of all gynecological cancers. Case report: An 86-year old woman with a history of several years of genital pruritus and many consultations for this reason, prior treatments included valacyclovir for genital herpes; topical corticosteroids and tachrolymus for lichen sclerosus et atrophicus (LEA) with poor response. She presented with pruritus and new vulvar lesions. Physical examination showed two ulcerated nodules on the left periclitorid region and the introitus. The biopsy confirmed an infiltrating well-differentiated SCC. CT-scans discarded metastases. She received 7 weeks of radiotherapy. Due to persistence of the tumor the patient entered palliative care. Two years afterwards the patient is in good condition. Discussion: SCC represents 95% of vulvar malignancies. There are 2 types: SCC in young women, associated with high-risk human papilloma virus infection and SCC in elder women associated to the preexistence of LEA. 45-61% of vulvar SCC is associated in with preexisting

Use of Mohs Technique and Immediate Reconstruction for Advanced Head and Neck Cutaneous Squamous Cell Carcinoma

Objectives: (1) Report the outcome of patients with cutaneous squamous cell carcinoma (SCCs) of the head and neck treated with Mohs micrographic surgery in the operating room. (2) Describe the method and benefits of a single operation for extirpation of cutaneous SCC and reconstruction in the operating room with the use of intraoperative Mohs margins. Methods: A total of 104 patients with cutaneous SCCs of the head and neck were retrospectively reviewed in a single-center retrospective study, considering recurrence, metastasis, and death between January 2002 and December 2008. The secondary aim was to describe the demographic and tumor characteristics, type of closure of defect, adjuvant therapies, immunocompromised status, bony or perineural invasion, and regional and local recurrence of SCC cases. Results: Twenty-one (20%) of the lesions were recurrent SCC. Ten (10%) patients had bony or perineural invasion. Additional extirpative procedures performed by the head and neck surgeons included 8 bone excisions (8%), 2 parotidectomies and neck dissections (2%). Eleven percent had local and 13% had regional recurrences. Nine percent of the total patient population died of disease. Disease-specific survival was 88%. Conclusions: Mohs micrographic surgery in the operating room for high-risk cutaneous SCC is effective. Using Mohs technique in the operating room permits a combined extirpation and reconstruction as a single procedure. This approach combines Mohs’ proven superior ability to produce clear margins with immediate reconstruction offered by the same surgeon. This offers patients many benefits, and extirpation with forethought of reconstruction offers potential superior outcomes, reduced hospitalizations and anesthetic exposures, and patient convenience.

Postoperative Chemoradiotherapy and Cetuximab for High-Risk Squamous Cell Carcinoma of the Head and Neck: Radiation Therapy Oncology Group RTOG-0234

To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features. Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m(2) or docetaxel 15 mg/m(2) once per week. Between April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors. Grade 3 to 4 myelosuppression was observed in 28% of patients in the cisplatin arm and 14% in the docetaxel arm; mucositis was observed in 56% and 54%, respectively. DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial (Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck), which had a hazard ratio of 0.76 for the cisplatin arm versus control (P = .05) and 0.69 for the docetaxel arm versus control (P = .01), reflecting absolute improvement in 2-year DFS of 2.5% and 11.1%, respectively. The delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial.

Sentinel node biopsy for high-risk cutaneous squamous cell carcinoma

AimThe use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the usefulness of and indication criteria for SNB for cutaneous SCC. Materials and methodsTwenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method. ResultsOf the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis (p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively (p = 0.016). ConclusionsSNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.

Basal Cell Carcinomas of the Vulva

Basal cell carcinoma (BCC) of the vulva is rare and may be confused with the much more commonly encountered high-risk human papillomavirus (HPV)-related basaloid squamous cell carcinoma (SCC). The HPV status of BCCs is not well established. This study assesses the utility of p16 and BerEP4 expression patterns and high-risk HPV detection for distinction of these tumors. Thirteen cases of vulvar BCC were analyzed by immunohistochemistry for p16 and BerEP4 expression. HPV status was assessed by in situ hybridization (ISH) with a high-risk HPV wide-spectrum probe and HPV 16 and 18 type-specific probes. All tumors (13/13) demonstrated patchy p16 positivity, with <50% of tumor cells expressing p16 in all cases. None demonstrated the diffuse p16 expression characteristic of high-risk HPV-associated lesions. No high-risk HPV was detected by ISH (0/13). Eleven of 13 (85%) vulvar BCCs showed diffuse, intense expression of BerEP4. The 2 BerEP4-negative cases were notably squamatized. The lack of diffuse p16 expression and failure to detect high-risk HPV by ISH in vulvar BCCs indicate that these tumors are unrelated to high-risk HPV. Thus, these ancillary techniques, particularly p16 immunohistochemistry, are useful for distinguishing vulvar BCCs from basaloid forms of high-risk HPV-related vulvar SCC. BerEP4 expression can help in distinction of these tumors except in cases of BCC with extensive squamatization. Distinction of vulvar BCC from basaloid SCC is important because of differences in extent of surgical treatment for these entities.

Update on Evaluation and Management of High-Risk Squamous Cell Carcinomas

High-risk cutaneous squamous cell carcinomas have multiple adverse clinical and pathological features associated with increased risks of recurrence, metastasis, and death. Evaluation includes a thorough clinical and lymph node exam, proper identification of high-risk features, and appropriate imaging studies to evaluate the extent of spread. Multidisciplinary management focuses on local control with aggressive and complete surgical resection, with adjuvant radiation mostly reserved for tumors with perineural invasion, multiple high-risk features, or nodal disease. Chemotherapy options for distant and recurrent disease remain limited and understudied.

頭頸部扁平上皮がん術後再発高危険症例における術後化学放射線同時併用療法の検討（原著）

頭頸部扁平上皮がん術後再発高危険症例における術後化学放射線同時併用療法の検討（原著）

Suggested Excisional Margins for Cutaneous Malignant Lesions Based on Mohs Micrographic Surgery

Surgical excision of skin cancer is a common treatment, yet the proper surgical margin remains unclear. This study reviews data on lesions and their margins as defined by Mohs micrographic surgery. To review margins as defined by Mohs micrographic surgery. Retrospective review of data from patients with skin cancer. Academic medical center. All patients with nonmelanoma skin cancer. Size and final defect size were compared to calculate the margins needed. All lesions were categorized based on histologic characteristics. A total of 495 lesions were reviewed. All tumors and defects had precise measurements. The mean margins for low-risk basal cell carcinomas, high-risk basal cell carcinomas, low-risk squamous cell carcinomas, and high-risk squamous cell carcinomas were 2.4 mm, 3.7 mm, 2.6 mm, and 5.3 mm, respectively. Statistical differences in surgical margins were found between all low- and high-risk cancer types. Established high-risk zones (H-zone) for basal cell carcinoma and squamous cell carcinoma were not associated with larger margins. Margins required to excise completely 95% of all the low-risk basal cell carcinomas, high-risk basal cell carcinomas, low-risk squamous cell carcinomas, and high-risk squamous cell carcinomas, were 4.75 mm, 8 mm, 5 mm, and 13.25 mm, respectively. Differences are noted between low- and high-risk cutaneous lesions. When primary excision instead of Mohs micrographic surgery is the only option, the aforementioned margins may be considered guidelines. The relevance of this study is to guide future management and margins for primary excision. 3.

Mohs micrographic surgery miscellaneous indications

Mohs micrographic surgery (MMS) is a technique that allows examination of all surgical margins of the excised skin lesion. It is a well-established treatment for high-risk basal and squamous cell carcinomas yielding unsurpassed cure rates. MMS is also employed to treat melanomas and certain uncommon tumors such as dermatofibrosarcoma protuberans, microcystic adnexal carcinoma, Merkel cell carcinoma, sebaceous carcinoma, desmoplastic trichoepithelioma, extramammary Paget’s disease and atypical fibroxanthoma. This article will review the evidence for MMS in the management of these less common indications.

In situ photoimmunotherapy is ineffective in treating deeply invasive squamous cell carcinoma

In situ photoimmunotherapy (ISPI) can be a treatment option for selected cutaneous malignancies in patients who are not surgical candidates. We herein report the case of a large, ulcerating poorly differentiated squamous cell carcinoma (SCC) affecting the foot of an elderly woman with chronic arsenicosis. The tumor failed radiotherapy, intralesional methotrexate, and 5-aminolevulinic acid photodynamic therapy (PDT). Because the patient was reluctant to undergo amputation, the recurrent tumor was treated with ISPI using topical imiquimod application followed by PDT. Despite some initial improvement in the superficial part of the tumor, tumor invasion to the underlying bone was detected. This case illustrates the lack of efficacy of ISIP in treating a high-risk invasive SCC.

Two lipids based on lipidomics as novel biomarkers for early detection of squamous cell lung cancer.

11114 Background: Lipids play roles in membrane structure, energy storage, and signal transduction as well as lung cancer. Lipidomics, a new technology aims to measure all the lipids in a cell, has not been applied to diagnostic test development for a variety of cancer types. Here, we adopt lipidomics as a means to identify plasma lipid markers for the early detection of lung cancer and complement CT-based methods for lung cancer screening. Methods: Using mass spectrometry, we profiled 390 individual lipids in a training discovery cohort comprised of cohorts that were either at “high-risk” for lung cancer (n=22) and squamous cell carcinoma at early stages (n=22). Cases had a minimum of two years clinical follow-up and were matched in terms of race, sex, age and smoking status. Gain ratio feature selection and local weighted classification model were employed to find the best training classifier, which was further validated against an additional cohort, including high-risk individuals (n= 20) and squamous cell carcinoma patients (n=17). Results: In the training discovery stage, we found 20 distinct lipids that were significantly distributed between high-risk and cases of squamous cell carcinoma. We further defined a two lipid marker panel had a training accuracy at 95.5% sensitivity, 90.9% specificity and 95.2% AUC (Area under ROC curve). The validation accuracy against the additional cohort is 100.0% sensitivity, 90.0% specificity and 99.0% AUC (Table). The power for sample size we used in both discovery training and validation stages were over 90%. Conclusions: Using lipidomics we identified two lipid markers capable of discerning cases of squamous cell carcinoma from individuals at high risk for lung cancer, with a high sensitivity, specificity and accuracy. The markers maybe further developed as a quick, safe blood test for early diagnosis of squamous cell lung cancer and reduce unnecessary follow-up imaging or invasive procedures. [Table: see text]

Is postoperative adjuvant chemoradiotherapy necessary for high-risk oropharyngeal squamous cell carcinoma?

High-risk factors for recurrence of head and neck squamous cell carcinoma after surgical resection include involvement of ≥ 2 regional lymph nodes, extracapsular spread, and microscopic involvement of resected mucosal margins. Adjuvant chemoradiotherapy is thought to improve postoperative locoregional control and survival. In this paper, we evaluate the efficacy of adjuvant therapy for high-risk oropharyngeal squamous cell carcinoma (OPSCC) (i.e., with ≥ 2 lymph nodes, positive extracapsular spread, or positive margins). This is a retrospective analysis of 45 high-risk OPSCC patients who underwent surgery without adjuvant therapy (n = 19), with radiotherapy (n = 17), or with chemoradiotherapy (n = 9). The median follow-up period was 41.0 months. Radiotherapy patients showed a trend toward longer overall survival than patients without adjuvant therapy [hazard ratio (HR) = 0.32, p = 0.176]. However, overall survival for the chemoradiotherapy group seemed to be the same as that for the no adjuvant therapy group (HR = 0.79, p = 0.779). Multivariate analysis found that the relative risk of recurrence for patients without adjuvant therapy compared with any adjuvant therapy was 3.02 (p = 0.101). The relative recurrence risk in radiotherapy patients was 0.95 compared with that in chemoradiotherapy patients (p = 0.971). However, pathological T-stage was significantly associated with disease-free survival for high-risk OPSCC. Although the current study uses data from a small retrospective sample of patients, our results suggest that the addition of chemotherapy to radiotherapy may not be necessary as an adjuvant therapy for all high-risk OPSCC. A novel prognostic factor, such as pathological T-stage, should be considered for selecting those patients with high-risk OPSCC who would benefit from adjuvant therapy.

PO-054: Postoperative Concurrent Cisplatin Based Chemoradiation in High Risk Squamous Cell Carcinoma of Oral Cavity

PO-054: Postoperative Concurrent Cisplatin Based Chemoradiation in High Risk Squamous Cell Carcinoma of Oral Cavity

口腔扁平上皮癌術後ハイリスク群における3週毎シスプラチンを用いた化学放射線療法の検討

口腔扁平上皮癌術後ハイリスク群における3週毎シスプラチンを用いた化学放射線療法の検討

The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity

BackgroundThe aim of this study was to compare the outcomes of postoperative adjuvant concomitant chemoradiotherapy using two different schedules of cisplatin for patients with high-risk oral squamous cell carcinoma (OSCC).MethodsFrom Feb. 2008 to Aug. 2010, 55 patients with high-risk OSCC were included in this study. Patients were randomized into treatment groups that either received 100 mg/m2 cisplatin once every 3 weeks (arm A) or 40 mg/m2 cisplatin once per week (arm B). All patients were irradiated with 66 Gy in 33 fractions.ResultsOf the 50 eligible patients, 26 were assigned to arm A, and 24 were assigned to arm B. Both groups of patients received the same mean doses of radiotherapy and cisplatin. However, 88.5% of patients in arm A and 62.5% of those in arm B (p = 0.047) received ≥ 200 mg/m2 of cisplatin in total. The overall toxicity was significantly greater in arm B (p = 0.020), and all of the grade 4 toxicities occurred in patients in arm B.ConclusionsThree-weekly high-dose cisplatin treatment showed higher compliance, and lower acute toxicity compared to weekly low-dose cisplatin treatment.

Phase II Feasibility Trial of Adjuvant Chemoradiotherapy with 3-weekly Cisplatin for Japanese Patients with Post-operative High-risk Squamous Cell Carcinoma of the Head and Neck

The current standard of care for post-operative high-risk squamous cell carcinoma of the head and neck is concurrent chemoradiotherapy with a 3-weekly cycle of cisplatin (3W-CDDP/RT). In previous pivotal trials, the complete delivery rate of three cycles of cisplatin and radiation therapy was only ~60%. Here, we evaluated the feasibility and safety of 3W-CDDP/RT in a Japanese population. The study enrolled post-operative high-risk squamous cell carcinoma of the head and neck patients. High-risk factors were a microscopically incomplete resection, extracapsular extension and two or more lymph node metastases. Subjects received three cycles of cisplatin at a dose of 100 mg/m(2) concomitant with radiation therapy (66 Gy/33 Fr). From August 2006 to May 2009, 25 eligible subjects were accrued, including 13 males, with a median age of 59 years, Eastern Cooperative Oncology Group performance status 0/1 (18/7), Stage III/IVA/IVB/recurrent (1/18/1/5) and oral cavity/oropharynx/hypopharynx/larynx (17/4/3/1). Protocol completion rate was 80%. The lower limit of the one-sided 90% confidence interval was 66%, which met the predefined statistical criteria. Grade 3/4 acute and late toxicities were almost identical to those in previous pivotal trials. No treatment-related deaths were observed. With a median follow-up of 39 months, 14 have had progression and 10 have died. Estimated 3-year locoregional control rate, relapse-free survival and overall survival were 74, 43 and 60%, respectively. On univariate analysis, oral cavity cancer and a cumulative cisplatin dose below 240 mg/m(2) appeared to be poor prognostic factors. This is the first Phase II feasibility trial of adjuvant chemoradiotherapy with 3-weekly cisplatin for post-operative high-risk squamous cell carcinoma of the head and neck in a Japanese population. This treatment was feasible and the safety profile was identical to those in pivotal Phase III trials.

Long-term Follow-up of the RTOG 9501/Intergroup Phase III Trial: Postoperative Concurrent Radiation Therapy and Chemotherapy in High-Risk Squamous Cell Carcinoma of the Head and Neck

Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes. A total of 410 analyzable patients who had high-risk resected head-and-neck cancers were prospectively randomized to receive either radiation therapy (RT: 60 Gy in 6 weeks) or identical RT plus cisplatin, 100 mg/m(2)i.v. on days 1, 22, and 43 (RT + CT). At 10 years, the local-regional failure rates were 28.8% vs 22.3% (P=.10), disease-free survival was 19.1% vs 20.1% (P=.25), and overall survival was 27.0% vs 29.1% (P=.31) for patients treated by RT vs RT + CT, respectively. In the unplanned subset analysis limited to patients who had microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% vs 21.0% (P=.02), disease-free survival was 12.3% vs 18.4% (P=.05), and overall survival was 19.6% vs 27.1% (P=.07), respectively. At a median follow-up of 9.4 years for surviving patients, no significant differences in outcome were observed in the analysis of all randomized eligible patients. However, analysis of the subgroup of patients who had either microscopically involved resection margins and/or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy. The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT.