Recurrent Squamous Carcinoma Research Articles

752P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic squamous cell cervix carcinoma: Subgroup analysis of the PEVOsq basket trial

752P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic squamous cell cervix carcinoma: Subgroup analysis of the PEVOsq basket trial

Рецидивирующее течение плоскоклеточного рака кожи у пациента с дистрофическим типом буллезного эпидермолиза

The development of squamous cell skin carcinoma (SCCC) is one of the most common complications in the junctional and dystrophic form of epidermolysis bullosa. Currently, early detection and surgery is the gold standard for treatment of skin tumors. However, detection of SCCC in patients with epidermolysis bullosa is a challenge even for an experienced clinician. In addition, there are nuances of performing a surgery, as well as postoperative care in these patients. In this article, we would like to share a rare experience of treatment of recurrent squamous cell skin carcinoma in young patient with recessive dystrophic epidermolysis bullosa.

Life-threatening bleeding after pelvic exenteration for recurrent cervical cancer: endovascular management of ruptured external iliac artery pseudoaneurysm: a case report and literature review

Background: Clinically, postoperative pseudoaneurysm rupture following gynecological radical surgeries is a very rare but fatal complication. The occurrence of this fatal complication should arouse the concern of clinicians. Accurate diagnosis and immediate treatment is needed for this emergency condition. Case: A 56-year-old women had life-threatening bleeding caused by ruptured external iliac artery pseudoaneurysm five months after pelvic exenteration for recurrent cervical squamous carcinoma. Emergency left external iliac artery covered stent placement was successfully performed to control the massive bleeding. The patient recovered well and no complication was observed during a three month follow-up period. Conclusions: In some cases, endovascular techniques may be an attractive alternative.

IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer

Background: A combination therapy with immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has become the first-line treatment for recurrent or metastatic head and neck squamous carcinoma (HNSCC). Although steroids are often used as anti-emetic medications during chemotherapy, their adverse effects on immune-combined chemotherapy are unclear in HNSCC.Methods: The effects of dexamethasone on tumor growth and immune cell population were evaluated in a mouse HNSCC model treated with PD-1 blockade combined with cisplatin. The effect of various doses of dexamethasone on cell proliferation, survival, surface markers, IFN-γ production, and antitumor effects in antigen-specific T cells was examined in vitro. The recovery of T cell dysfunction by IL-2 was assessed in vitro and in vivo.Results: In a mouse HNSCC model, dexamethasone showed limited antitumor effects on immunochemotherapy. Dexamethasone decreased the number of T cells and inhibited T cell differentiation into effector and central memory T cells. In the in vitro assessment, dexamethasone induced cell death, limited proliferation, and reduced the reactivity against HNSCC cell lines of antigen-specific T cells in a dose-dependent manner. The expression of inhibitory receptors on T cells was not affected by steroids. This inhibition was recovered by IL-2 and IL-2/anti-IL-2 complexes (IL-2 Cx) in vitro and in vivo, respectively.Conclusion: Our preclinical data indicate that dexamethasone diminishes the antitumor effects of immunochemotherapy in patients with HNSCC. IL-2 Cx recovered the inhibition of antitumor immunity by steroids and might be a potent immune adjuvant for patients who require steroids during PD-1 blockade and chemotherapy.

Long-Term Safety and Efficacy of CT-Guided I125 Radioactive Seed Implantation as a Salvage Therapy for Recurrent Head and Neck Squamous Carcinoma: A Multicenter Retrospective Study.

PurposeTo investigate the safety and efficacy of CT-guided I125 radioactive seed implantation (RSI) as a salvage therapy for recurrent head and neck squamous carcinoma (rHNSC) after external beam radiotherapy (EBRT) or surgery.Materials and MethodsThis is a multicenter retrospective study of 113 patients (83 males; median age 57 years) with rHNSC who underwent CT-guided I125 RSI between February 2003 and December 2017. Of the included patients, 107 patients previously received EBRT and 65 patients received surgery and all were ineligible or rejected for salvage surgery and/or repeat EBRT.ResultsDuring a median follow-up duration of 20 months (range, 3-152 months), 87 patients died. The 1-, 2-, 3-, and 5-year local control rate were 57.4%, 41.8%, 29.3%, and 15.2%, respectively. The median time to progression was 15 months [95% confidence interval (CI), 6.1-23.9 months]. The median overall survival (OS) was 20 months (95% CI, 12.4-27.6 months). The 1-, 2-, 3-, and 5-year OS rate were 63.6%, 44.6%, 29.9%, and 21.7%, respectively. Univariate and multivariate analyses revealed that KPS score and postoperative D90 were significantly associated with patients’ OS. The complications were mainly grade I/II skin and mucosal reactions: 18 cases (15.9%) of grade I/II and eight cases (7.0%) of grade III radiation dermatitis, and 14 cases (12.4%) of grade I/II and three cases (2.7%) grade III mucosal reactions. No grade IV or severer complications were found.ConclusionCT-guided I125 RSI may be safe as a salvage therapy for rHNSC after EBRT/surgery, yielding promising efficacy compared with historical data. KPS score and postoperative D90 may be significantly associated with OS.

MSOR02 Presentation Time: 10:05 AM: Preliminary Results of 3D Printing Individual Template Assisted CT-Guided Radioactive I-125 Seed Interstitial Brachytherapy as a Salvage Therapy for Recurrent Head and Neck Squamous Carcinoma after External Beam Radiotherapy

Objective: To investigate the safety and efficacy of 3D-printing non-co-planar template (3D-PNCT)-assisted CT-guided radioactive I-125 seed (RIS) interstitial brachytherapy in the treatment of recurrent head and neck squamous carcinoma after external beam radiotherapy.

MSOR02 Presentation Time: 10:05 AM: Preliminary Results of 3D Printing Individual Template Assisted CT-Guided Radioactive I-125 Seed Interstitial Brachytherapy as a Salvage Therapy for Recurrent Head and Neck Squamous Carcinoma after External Beam Radiotherapy

MSOR02 Presentation Time: 10:05 AM: Preliminary Results of 3D Printing Individual Template Assisted CT-Guided Radioactive I-125 Seed Interstitial Brachytherapy as a Salvage Therapy for Recurrent Head and Neck Squamous Carcinoma after External Beam Radiotherapy

Established treatment concepts for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSSC)

Recurrent and metastatic squamous cell carcinomas of the head and neck are still difficult to treat. The EXTREME regimen has been the standard of care for the last decade, but recent studies initiated a change. In this work we provide an overview of the established treatment concepts for recurrent and metastatic squamous cell carcinomas of the head and neck with palliative intent. We performed a literature search using the key words: recurrent, metastatic, cancer, head and neck, HNSCC, treatment, chemotherapy, immunotherapy, salvage, and surgery. Furthermore, the presentations of the ASCO highlights of head and neck cancer from 2019 and 2020 were included. The KEYNOTE-048 and the TPEx randomized trial are the most relevant trials in the first line setting. The CheckMate 141 and KEYNOTE-040 have the greatest impact for the second line regimen. The expression of PD-L1, prior treatment, performance status, local symptoms and tumor burden are the most important factors regarding choice of treatment. Pembrolizumab alone or in combination with chemotherapy can be recommend as the 1st line standard in patients with combined positive score (CPS) ≥20. The choice of therapy in patients with CPS 1-19 and CPS <1 has to be individually evaluated for each patient. Furthermore, TPEx is an encouraging alternative to the EXTREME regimen with less toxicity and improved quality of life.

Loss of MHC Class I Expression in HPV-associated Cervical and Vulvar Neoplasia

Tumor cell expression of major histocompatibility complex (MHC) class I is required for antigen presentation and adaptive immune recognition. Absent or diminished MHC class I expression is thought to contribute to immunotherapeutic resistance in some epithelial tumors but has not been previously studied in cervical and vulvar carcinoma. Given that anti-programmed cell death 1 (PD-1) checkpoint inhibition is deployed for programmed cell death ligand 1 (PD-L1)-positive recurrent and metastatic cervical squamous carcinomas, identifying tumors with loss of MHC class I is of clinical interest to optimize the selection of immunotherapeutic candidates. Immunohistochemistry for PD-L1 and MHC class I combined A, B, and C heavy chains (MHC class I) was assessed in 58 human papillomavirus-associated cervical and vulvar lesions, including 27 squamous intraepithelial lesions (SILs) and 31 invasive squamous cell carcinoma (SCC). Although 84% of SCC and 22% of SIL were PD-L1-positive, 35.5% (11/31) of SCC and 18.5% (5/27) of SIL also showed clonal or complete loss of MHC class I. Loss of MHC class I expression was more common in PD-L1-positive (10/26, 38%) versus PD-L1-negative SCC (1/5, 20%). In summary, over one third of human papillomavirus-associated cervical and vulvar SCC show clonal or complete loss of MHC class I expression, including many PD-L1-positive cases. This suggests that the efficacy of checkpoint inhibitors targeting the PD-1/PD-L1 axis may be limited in a subset of cervical and vulvar squamous neoplasms due to an impaired ability to engage with the adaptive immune system related to loss of MHC class I expression.

Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Intraoperative Chemotherapy (Hipec) for Recurrent Squamous Cell Carcinoma of the Pancreas

Background/Aims: Squamous cell carcinoma of the pancreas is a rare entity and its histogenesis is not adequately understood. Surgical resection is the only potentially curative option. Recurrent local-regionally pancreatic carcinomas are usually inoperable and are treated with palliative intent. The purpose of the study is to present the treatment strategy of a recurrent squamous cell pancreatic carcinoma with peritoneal carcinomatosis. Case Report: A 49-year-old man with local-regional recurrent squamous cell pancreatic carcinoma underwent complete (CC-0) cytoreductive surgery (CRS) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). In a 6-month time he underwent secondary CRS+HIPEC for regional recurrence. Despite treatment with adjuvant systemic chemotherapy the patient died 12 months after the initial CRS with osseous metastases. Conclusions: A reliable prognosis for recurrent squamous cell pancreatic carcinoma is impossible despite complete cytoreduction in combination with HIPEC and systemic chemotherapy.

Prognostic analysis of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgical treatment

Objective To evaluate the clinical efficacy and prognostic factors of recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Methods From December 2011 to December 2015, 152 cases of recurrent thoracic esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery were retrospectively analyzed. The overall survival (OS) after treatment failure, clinical efficacy and prognostic factors of different salvage treatments were analyzed. OS was calculated by Kaplan-Meier method. Prognostic analysis was performed by using multivariate Cox regression model. Results The median interval of the first recurrence was 10.6(2.0 to 69.1) months. The median OS after recurrence was 8.0(0.8 to 43.3) months. The 1-, 2-and 3-year OS rates after recurrence were 36.0%, 15.1% and 5.2%, respectively. The median OS of patients with locoregional recurrence alone, distant metastasis alone and locoregional recurrence combined with distant metastasis was 11.3(1.8 to 43.3) months, 6.7(1.2 to 28.6) months and 5.1(0.8 to 22.9) months, respectively. Multivariate analysis demonstrated that neoadjuvant chemotherapy (P=0.009), ypTNM stage (P=0.012), comprehensive treatment after recurrence (P=0.000) and locoregional recurrence (P=0.026) were independently correlated with the OS of patients with recurrent esophageal squamous cell carcinoma. Conclusions Neoadjuvant therapy, ypTNM stage, recurrence pattern and post-recurrence treatment are the independent risk factors for clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy combined with surgery. Clinical prognosis of patients with recurrent esophageal squamous cell carcinoma after neoadjuvant therapy is not satisfactory. After recurrence, combined treatment mode should be adopted according to the site of recurrence and neoadjuvant treatment mode to maximize the benefits of salvage treatment. Key words: Esophageal neoplasm, recurrent/ neoadjuvant treatment; Locoregional recurrence; Distant metastasis; Prognosis

A Unique Case of Atezolizumab-Induced Autoimmune Diabetes

Immunotherapy is a novel treatment that can cause autoimmune diabetes in rare cases. More cases occur following use of the inhibitor to the protein programmed cell death-1 rather than the inhibitor to programmed cell death-ligand 1. We report a unique case of autoimmune diabetes following atezolizumab use. A 55-year-old, Aboriginal Australian female with no prior history of diabetes was commenced on atezolizumab for recurrent squamous cell lung carcinoma. Two months following its commencement, there was the onset of fatigue, polyuria, polydipsia, and new hyperglycemia. Subsequently she was found to have a borderline-low C peptide level of 0.6 nmol/L (reference range is 0.5 to 1.0 nmol/L), and positive zinc transporter-8 antibodies. Following the diagnosis of autoimmune diabetes, 5 units of glargine insulin was commenced which maintained euglycemia and resolved her symptoms of hyperglycemia. There are few case reports of atezolizumab-induced autoimmune diabetes. We present the first case associated with zinc transporter-8 antibodies, and a unique case of autoimmune diabetes in a patient of Aboriginal Australian background.

P223 BILATERAL RECURRENT LARYNGEAL NERVE LYMPHADENECTOMY DURING THORACOSCOPIC ESOPHAGECTOMY IN PRONE POSITION

Abstract Aim To present a video of a complete bilateral recurrent laryngeal nerve lymphadenectomy performed during minimally invasive esophagectomy using thoracoscopic video-assisted surgery in the prone position. Background and Methods Surgical treatment for esophageal cancer needs detailed lymphadenectomy. Indeed, the number of surgically dissected lymph nodes is important for staging accuracy and also determines patient’s prognosis, including those along the recurrent laryngeal nerve. However, recurrent laryngeal nerve dissection remains difficult and increases the appearance of postoperative complications. This is a video of a bilateral recurrent laryngeal nerve lymphadenectomy during thoracoscopic esophagectomy performed in the prone position in a female patient with esophageal cancer. Results A 75 year-old female was diagnosed with recurrent squamous cell middle third esophageal carcinoma. The patient had first been diagnosed eleven years ago, receiving chemoradiotherapy as a radical treatment. The patient achieved a complete response after treatment, which remained for eleven years. Eleven years later, during routine follow-up, tumor recurrence was identified in the middle third of the esophagus. After presentation in a Multidisciplinary Group the patient underwent minimally invasive McKeown esophagectomy. First, a video-assisted thoracoscopic surgery was performed in the prone position to mobilize the thoracic esophagus and complete a detailed mediastinal lymph node dissection, including infra-carinal lymph nodes, bilateral bronchial lymph nodes and also bilateral recurrent laryngeal nerve lymph nodes. Afterwards, the abdominal esophagus and lymph node dissection is performed using a laparoscopic approach, and also a left cervicotomy in the supine position. An assistance laparotomy was made to externalize the specimen and make the gastric conduit. A manual end-to end esophago-gastric anastomosis was executed and finally, a feeding jejunostomy tube was placed. The patient presented a benign postoperative course, introducing enteral nutrition and oral intake developing no complications, such as dysphonia, nor dysphagia and was discharged on the 8th postoperative day. The postoperative barium swallow radiography showed no leaks nor other complications and pathology report confirmed tumor free resection margins. Conclusion Detailed mediastinal lymph node dissection and exhaustive bilateral recurrent laryngeal nerve lymphadenectomy can be safely performed by minimally invasive surgery, as is shown in the video. The technique shown is feasible, achieves a complete lymph-node dissection and avoids postoperative complications such as dysphonia and recurrent laryngeal nerve palsy.

Significance of Malignant Peritoneal Cytology on the Survival of Women with Early-Stage Cervical Cancer: A Japanese Gynecologic Oncology Group Study

This study examined the association between peritoneal cytology and survival in early-stage cervical cancer. This is a nationwide multicenter retrospective study, examining consecutive women with clinical stage IB1-IIB cervical cancer who underwent radical hysterectomy with available peritoneal cytology results from 2004–2008. Propensity score inverse probability of treatment weighting was used to assess the impact of malignant peritoneal cytology on survival. Among 1409 analyzed cases, 88 (6.2%) had malignant peritoneal cytology. On weighted models, malignant peritoneal cytology was associated with decreased disease-free survival (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.36–2.32) and overall survival (OS, HR 1.93, 95% CI 1.44–2.59). On sensitivity analyses, malignant peritoneal cytology was associated with decreased OS in adenocarcinoma/adenosquamous carcinoma, high-risk early-stage disease and those who received concurrent chemo-radiotherapy. However, among women who received postoperative systemic chemotherapy, malignant peritoneal cytology was not associated with OS (HR 1.21, 95% CI 0.72–2.04). A systematic review, including our results, showed that malignant peritoneal cytology was associated with decreased OS (HR 4.03, 95% CI 1.81–8.99) and increased recurrence in squamous carcinoma (odds ratio 1.89, 95% CI 1.05–3.39) and adenocarcinoma (odds ratio 4.30, 95% CI 2.30–8.02). In conclusion, the presence of malignant cells in peritoneal cytology is associated with decreased survival in early-stage cervical cancer. The possible benefit of systemic chemotherapy in this subgroup merits further investigation.

Analysis of prognostic factors and therapeutic patterns of recurrent stage Ⅰb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy

Objective: To analyze the prognosis and appropriate treatment modalities of the patients with recurrence of early stage (Ⅰb-Ⅱa) cervical squamous cancer primarily treated with radical hysterectomy. Methods: This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb and Ⅱa recurrent cervical squamous cancer who underwent radical hysterectomy primarily from January 2007 to July 2015. Kaplan-Meier method and Cox regression analysis were performed to analyze related prognostic factors of overall survival and progression-free survival, which included age, postoperative therapy, the site of recurrence, therapy-free interval (TFI) and treatment modality. The patients who were treated with palliative chemotherapy after recurrence were selected as a subgroup. The responses of palliative chemotherapy were evaluated and analyzed among different factors, included TFI, the site of recurrence and chemotherapy regime. Results: Of the 2 071 patients, 116 relapsed Ⅰb-Ⅱa cervical squamous cancer were included in the study with the average age of (45.6±7.2) years old. 3-year progression-free survival rate and 3-year overall survival rate after recurrence were 30.2% and 42.2%, respectively. Univariate analysis implied that postoperative radiotherapy, recurrence site, TFI and treatment modality were associated with progression-free survival (P<0.05), while postoperative radiotherapy, TFI and treatment modality with overall survival (P<0.05). Multivariate analysis showed that TFI and treatment modality were independent prognostic factors for progression-free survival (P<0.05), while postoperative radiotherapy at initial treatment, TFI and treatment modality were independent prognostic variables for overall survival (P<0.05). In the analysis of treatment modality, 3-year progression-free survival rate and 3-year overall survival rate of 47 patients who were treated with definitive local therapy were significantly higher than that of 69 patients who were treated with palliative chemotherapy (P<0.01). In the subgroup analysis of palliative chemotherapy, 15 patients achieved complete response (21.7%) and 16 displayed partial response (23.2%). The overall response rate (ORR) was 44.9%. TFI (P<0.01) and chemotherapy regime (P<0.05) were significant factors associated with ORR. The ORR of TFI ≥12 months was significantly higher than that of TFI <12 months. Besides, the ORR of paclitaxel plus platinum chemotherapy was prominently higher than that of other regimens, while there was no significant difference between the ORR of paclitaxel plus cisplatin and other platinum (P=0.408). Conclusions: For recurrent stageⅠb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy, use of definitive local therapy for suitable patients is advised to achieve better prognosis. In terms of palliative chemotherapy, longer TFI may mean better ORR and the combination of paclitaxel plus platinum is preferred.

Prevention of severe toxicity of fluoropyrimidines-based chemotherapy due to DPD deficiency: External quality evaluation of uracil and dihydrouracil measurements in plasma

Severe late toxicity is common after re-irradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck. However, many patients experience complications from tumor progression before manifesting late effects. We constructed a nomogram to examine this relationship between late toxicity and competing risks.Patients with RSP squamous carcinoma originating in a field previously irradiated to ≥40 Gy and treated with IMRT-based re-irradiation to ≥40 Gy were collected. Grade ≥3 late toxicity developing ≥90 days after re-irradiation was collected. A multivariable competing-risk model was fit to the actuarial risk of late toxicity with progression or death as the competing risk. The final bootstrap optimized model was converted into a nomogram.From 9 institutions, 505 patients were included. The 2-year incidence of grade ≥3 late toxicity was 16.7% (95% CI 13.2–20.2%) whereas progression or death was 64.2% (95% CI 59.7–68.8%). The median freedom from late toxicity, progression or death was 10.7, 5.5 and 3.2 months for RPA class I-III patients respectively, whereas the median OS was 44.9, 15.9 and 7.9 months, respectively. The final model included six clinical factors. Notably, dose, volume and fractionation did not significantly impact toxicity.After re-irradiation, the risk of progression or death is approximately four times the risk of radiation-related severe late toxicity. The risk of late toxicity may be more dependent on patient and disease factors than modifiable treatment factors. This model is useful for patient selection, pre-treatment consent and post-treatment survivorship following re-irradiation.

Successful multidisciplinary treatment including repeated metastasectomy for recurrent squamous cell esophageal carcinoma: a case report

BackgroundRecurrences after radical esophagectomy are common. The prognosis for recurrent esophageal cancer is generally poor. Recurrences usually occur between 1 and 3 years of surgery, with the duration of median survival after recurrence ranging from 5 to 10 months. The number of sites and involved organs vary among patients. Consequently, a standard therapeutic strategy has not been established, and the role of surgery in the management of recurrence is unclear.Case presentationA 67-year-old man presented with dysphagia 6 months previously and was diagnosed with esophageal squamous cell carcinoma (ESCC) in the upper thoracic region (T2M0M0, stage IB), for which he underwent thoracoscopy-assisted esophagectomy and lymphadenectomy. Adjuvant chemotherapy was not prescribed. Three years after the operation, he developed a solitary metastasis in the left lung, requiring segmentectomy followed by chemotherapy with combined cisplatin (CDDP) and 5-fluorouracil (5-FU). The following year, a metastatic lesion was recognized in the right lung, invading the chest wall, for which he underwent partial lobectomy with local chest wall resection. Multiple mediastinal and abdominal lymph node (LN) metastases were detected in the right lung a year later, which necessitated chemoradiation to a dose of 50.4 Gy with concomitant CDDP and 5-FU. Post-treatment computed tomography (CT) showed a good response. Positron emission tomography (PET)-CT revealed a reduction in the metastatic LNs with no fluoro-deoxy-glucose (FDG) uptake. The following year, metastases were detected in the left cervical LNs. Owing to the limited extent of metastases, resection was followed by chemoradiation to a dose of 50 Gy with CDDP and 5-FU. The following year, metastases were detected in the mediastinal LNs; chemotherapy was administered with nedaplatin and docetaxel. The follow-up CT and PET-CT demonstrated complete disappearance of the tumor, and the patient is currently surviving without recurrence for 11 years from the first curative operation.ConclusionsThis case demonstrates that aggressive multidisciplinary treatment including surgery and radiation to achieve local control could be a meaningful treatment strategy in cases with limited and slowly occurring recurrences.

A competing risk nomogram to predict severe late toxicity after modern re-irradiation for squamous carcinoma of the head and neck

PurposeSevere late toxicity is common after re-irradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck. However, many patients experience complications from tumor progression before manifesting late effects. We constructed a nomogram to examine this relationship between late toxicity and competing risks. Methods and materialsPatients with RSP squamous carcinoma originating in a field previously irradiated to ≥40 Gy and treated with IMRT-based re-irradiation to ≥40 Gy were collected. Grade ≥3 late toxicity developing ≥90 days after re-irradiation was collected. A multivariable competing-risk model was fit to the actuarial risk of late toxicity with progression or death as the competing risk. The final bootstrap optimized model was converted into a nomogram. ResultsFrom 9 institutions, 505 patients were included. The 2-year incidence of grade ≥3 late toxicity was 16.7% (95% CI 13.2–20.2%) whereas progression or death was 64.2% (95% CI 59.7–68.8%). The median freedom from late toxicity, progression or death was 10.7, 5.5 and 3.2 months for RPA class I-III patients respectively, whereas the median OS was 44.9, 15.9 and 7.9 months, respectively. The final model included six clinical factors. Notably, dose, volume and fractionation did not significantly impact toxicity. ConclusionsAfter re-irradiation, the risk of progression or death is approximately four times the risk of radiation-related severe late toxicity. The risk of late toxicity may be more dependent on patient and disease factors than modifiable treatment factors. This model is useful for patient selection, pre-treatment consent and post-treatment survivorship following re-irradiation.

Higher efficacy and complete response with administration of eribulin for recurrent squamous cell breast carcinoma: A case report.

Squamous cell carcinoma is a rare histological type of breast cancer classified as metaplastic carcinoma. Metaplastic carcinoma involves differentiation of the breast glandular duct cells into mesenchymal tissues. While the chemotherapy regimen for metaplastic carcinoma is often similar to that for invasive ductal carcinoma, recurrence is associated with a poor prognosis due to the inadequate therapeutic efficacy of the regimen. We herein present the case of a 42-year-old female patient who underwent mastectomy of the right breast and right axillary node lymphadenectomy for T4N3aM0 breast cancer stage. The cancer was histopathologically diagnosed as squamous cell carcinoma of the breast. Adjuvant cyclophosphamide-epirubicin-fluorouracil (CEF) postoperative chemotherapy was administered, and lymphadenectomy of right-sided parasternal lymphatic metastases with pleural drainage was subsequently performed. Radiotherapy was administered to the thoracic wall and supraclavicular lymph nodes at 60 Gy. Positron emission tomography (PET)-computed tomography (CT) examination 3 months after the radiotherapy identified accumulation of fluorodeoxyglucose (FDG) in a supraclavicular lymph node and the thoracic wall; hence, a chemotherapeutic regimen with eribulin was initiated. At 11 months after initiation of eribulin, complete response was achieved, indicated by the absence of FDG accumulation in both the supraclavicular lymph node and the thoracic wall on PET-CT. The treatment efficacy of eribulin is considered to be a result of the mixed morphology of squamous cell carcinoma, including the presence of an epithelial component, such as adenocarcinoma cells, and a mesenchymal component, in the form of sarcomatoid cells. Eribulin displayed an effect similar to that of adriamycin against malignant soft tissue tumors and was shown to effectively target mesenchymal components. In cases of reduced expression of the DNA repair pathway components, such as in metaplastic carcinomas, eribulin may be more effective compared with adriamycin, the mechanism of action of which involves inhibition of DNA synthesis. A superior therapeutic effect was obtained with eribulin in squamous cell carcinoma. Therefore, eribulin appears to be a promising, effective therapeutic choice for the management of metaplastic carcinomas, including squamous cell carcinomas.

Nivolumab (nivo) vs investigator’s choice (IC) in patients (pts) with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Analysis of CheckMate 141 by age.

6028Background: Nivo is the only immunotherapy to significantly improve overall survival (OS) in pts with platinum (plt)–refractory R/M SCCHN. In the randomized, open-label, phase 3 CheckMate 141 t...