Untreated Squamous Cell Carcinoma Research Articles

Tyrosine-Like Crystalloids Localize to Non-Neoplastic True Vocal Cord and Attachments.

Tyrosine-rich or tyrosine-like crystalloids (TC) were initially described in salivary gland pleomorphic adenoma. The presence of TC in non-neoplastic tissues is rare, and it has been reported exclusively in the larynx. This study aims to characterize the frequency and anatomical localization of TC in total laryngectomy specimens. Review of consecutive laryngectomy specimens in which the cassette summary documented parasagittal section sampling of the right and left vocal folds and the anterior commissure. Data collected included patient demographics, underlying diagnoses, history of radiation therapy, presence, and location of TC. Of 86 laryngectomy specimens, 16 (19%) contained amphophilic to eosinophilic TC. The study cohort included 11 males and 5 females, aged 37 to 85 years (mean 62, median 63). Laryngectomy surgery was performed for advanced untreated squamous cell carcinoma (SCCa) (7/16, 43.75%), recurrent post-treatment SCCa (7/16, 43.75%), previously untreated laryngeal large cell neuroendocrine carcinoma (1/16, 6.25%), and non-functional larynx post-chemoradiation (1/16, 6.25%). According to the macroscopic cassette summary, TC were predominantly found in the anterior commissure Sect.(13/16, 81.25%), with fewer cases in sections containing the left (2/16, 12.5%) or the right (1/16, 6.25%) vocal folds. Microscopically, TC localized to the anterior macula flava and/or adjacent vocal ligament (12/16, 75%) and the anterior commissure tendon (4/16, 25%). TCs are predominantly reported as admixed with a neoplasm, however this study confirms that TC can also occur in non-neoplastic tissues of the larynx. There was no clear relationship between the presence of TC and prior radiation therapy. TC in the specialized connective tissues of the macula flava and true cord tendinous insertions distinct from tumor may form in response to alterations in mechanical stress, though an age-related change within the spectrum of normal laryngeal microanatomy also remains a possibility.

Successful 10-year outcomes after supracricoid partial laryngectomy for selected glottic squamous cell carcinoma classified as T3N0M0: A STROBE analysis

PurposeTo evaluate long-term oncological outcome for patients with selected glottic squamous cell carcinoma (SCC) classified as T3N0M0 treated by supracricoid partial laryngectomy (SCPL). Materials and methodsAnalysis of an inception cohort of 46 patients with isolated untreated SCC classified as T3N0M0 and minimum 10-year follow-up, consecutively treated by SCPL between 1982 and 2012 in a French university teaching hospital. The main endpoint was 5- and 10-year actuarial survival and local control estimates. Accessory endpoints comprised cause of death, screening for variables decreasing survival and increasing risk of local recurrence, oncologic consequences of local recurrence, and laryngeal preservation rate. ResultsFive- and 10-year actuarial survival was 78.1%, and 53.3%, respectively. The main causes of death were intercurrent disease and metachronous second primary, each in 33.3% of cases. Postoperative mortality (aspiration pneumonia) was 2.1%. There were no significant correlations between survival and any study variables. Five- and 10-year local control was 90.5%. Overall local recurrence varied significantly (P=0.003), from 2.3% with negative margins (R0) to 100% with positive margins (R1) and/or dysplasia. Local recurrence was associated with a significantly (P<0.005) increased risk of nodal failure and distant metastasis, and reduced survival. Overall laryngeal preservation was 89.1%. ConclusionThe present results suggest that SCPL should continue to be taught and that this type of partial laryngeal surgery should be included in the various organ-sparing strategies considered in advanced laryngeal cancer.

Head and neck squamous cell carcinoma: evaluation of iodine overlay maps and low-energy virtual mono-energetic images acquired with spectral detector CT

To evaluate the diagnostic value of spectral detector computed tomography (SDCT)-derived iodine overlay maps and low-energy virtual mono-energetic images (VMI) for the initial locoregional assessment of primary, therapy-naive head and neck cancer. Fifty-six patients with histologically confirmed untreated squamous cell carcinoma of the head and neck who underwent SDCT of the neck for staging purposes were included in this retrospective study. Attenuation, image noise as well as signal- and contrast-to-noise ratios (S-/CNR) in VMI40-70keV were obtained from region of interest (ROI)-based measurements in the tumour and important anatomical landmarks (sternocleidomastoid muscle, subcutaneous fat, thyroid gland, submandibular gland, carotid artery, and jugular vein). Tumour conspicuity and delineation, as well as subjective image quality, were rated for conventional images, VMI40-70keV, and iodine overlay maps using five-point Likert scales. The CNR of the tumour versus the floor of the mouth and the CNR of the tumour versus the sternocleidomastoid muscle was significantly higher in VMI40keV in comparison to conventional images (10.0±7.3 versus 3.8±3.3 and 11.3±7.6 versus 3.6±2.8; p<0.05 each). This was supported by qualitative results, as tumour conspicuity and delineation received superior ratings in iodine overlay maps and VMI40keV compared to conventional images (5 [3-5] and 5 [4-5] versus 3 [2-5]; 5 [2-5] and 5 [3-5] versus 3 [2-4], respectively, all p<0.05). VMI40keV yielded the highest score among all included image reconstructions for overall image quality (p<0.05 all). Iodine overlay maps and low-energy VMI derived from SDCT improve initial assessment of primary squamous cell carcinoma of the head and neck compared to conventional images.

Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma.

We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis. Neoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery. Preoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil.

Central neck lymph node metastasis in oral squamous cell carcinoma at the floor of mouth

sBackgroundOur goal was to analyze the incidence of level VI metastasis in previously untreated oral squamous cell carcinoma (SCC) patients and their clinicopathological and prognostic characteristics.MethodsOral SCC patients with level VI metastasis were retrospectively enrolled, and their demographic and pathologic features as well as their survival data were descriptively analyzed.ResultsA total of 13 cases from 1875 patients were included, all patients had SCC at the floor of mouth (SCCFOM). Eight (61.5%) patients had a pT4 tumor, and all patients had a pathological N3 neck with multiple positive lymph nodes. Adverse pathologic features were present in 100% of the patients. The size of the metastatic foci in level VI ranged from 2.6 cm to 4.5 cm with a mean value of 3.2 cm, and 5 patients showed a soft tissue deposit with no lymph node component. Recurrence occurred in all patients, and 11 patients died of uncontrolled cancer within 5 years after surgery.ConclusionLevel VI metastasis in primary oral SCCFOM is rare, and its prognosis is poor.

Comparison of daily low dose cisplatin versus weekly cisplatin concurrently with radiotherapy during head and neck cancer

Head and neck cancers can arise in the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid, and salivary glands and include a variety of histopathologic tumours. Squamous cell cancer (SCC) is the most common pathological type of head and neck cancer.This is prospective, Observational and comparative study.The diagnosis of untreated squamous cell carcinoma of the head and neck region, i.e., oral cavity, oropharynx, hypopharynx, or larynx in advanced stage III, IVA or IVB SCCHN was confirmed by a radiation oncologist prior to the initiation of the treatment. Patients were considered to comply with radiation treatment if they completed 70 Gy within 45 days. Chemotherapy compliance (six cycles in weekly or 28–30 cycles in daily cisplatin) were 63% and 73%, respectively. The primary reason for noncompliance toward chemotherapy (37% vs. 27% in weekly vs. daily Cisplatin studies, respectively) was due to the development of excessive toxicity. This also included those who left treatment midway (due to any reason) or died during therapy.Therefore, if an intensified treatment protocol has to be used, i.e. modest acceleration along with either “weekly” or “daily” cisplatin, both can be used, provided patients are selected properly and due attention is paid to timely and adequate supportive care.

Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma

Novel approaches are needed to improve outcomes in patients with squamous cell carcinoma of the oral cavity. Neoadjuvant immunotherapy given prior to surgery and combining programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibitors are 2 strategies to enhance antitumor immune responses that could be of benefit. In this randomized phase 2 clinical trial conducted at 1 academic center, 29 patients with untreated squamous cell carcinoma of the oral cavity (≥T2, or clinically node positive) were enrolled between 2016 to 2019. Treatment was administered with nivolumab, 3 mg/kg, weeks 1 and 3, or nivolumab and ipilimumab (ipilimumab, 1 mg/kg, given week 1 only). Patients had surgery 3 to 7 days following cycle 2. Safety and volumetric response determined using bidirectional measurements. Secondary end points included pathologic and objective response, progression-free survival (PFS), and overall survival. Multiplex immunofluorescence was used to evaluate primary tumor immune markers. Fourteen patients were randomized to nivolumab (N) and 15 patients to nivolumab/ipilimumab (N+I) (mean [SD] age, 62 [12] years; 18 men [62%] and 11 women [38%]). The most common subsite was oral tongue (n = 16). Baseline clinical staging included patients with T2 (n = 20) or greater (n = 9) T stage and 17 patients (59%) with node-positive disease. Median time from cycle 1 to surgery was 19 days (range, 7-21 days); there were no surgical delays. There were toxic effects at least possibly related to study treatment in 21 patients, including grade 3 to 4 events in 2 (N), and 5 (N+I) patients. One patient died of conditions thought unrelated to study treatment (postoperative flap failure, stroke). There was evidence of response in both the N and N+I arms (volumetric response 50%, 53%; pathologic downstaging 53%, 69%; RECIST response 13%, 38%; and pathologic response 54%, 73%, respectively). Four patients had major/complete pathologic response greater than 90% (N, n = 1; N+I, n = 3). With 14.2 months median follow-up, 1-year progression-free survival was 85% and overall survival was 89%. Treatment with N and N+I was feasible prior to surgical resection. We observed promising rates of response in both arms, supporting further neoadjuvant studies with these agents. ClinicalTrials.gov Identifier: NCT02919683.

Evaluation of robotic surgery for transoral resection of T1-2 squamous cell carcinoma of the tonsillar fossa

GoalTo evaluate transoral robotic surgery (TORS) for isolated previously untreated squamous cell carcinoma (SCC) of the tonsillar fossa classified as T1-2. MethodRetrospective analysis of two cohorts of isolated untreated T1-2 tonsillar fossa SCC consecutively operated on by a transoral approach, with (R=21) and without (NR=24) robotic assistance, in the period 2006–2014. Three main (survival, local control, and operative morbidity) and three secondary (pathologic data, incidence and duration of tracheotomy and nasogastric intubation, and hospital stay) endpoints were compared between groups. The significance threshold was set at P< .005. ResultsThree- and five-year actuarial survival estimates were 80.2% and 74.5% respectively in group R, and 91.5% and 82.5% respectively in group NR (NS: P=.34). Three- and five-year actuarial local control estimates were 90% and 90% respectively in group R, and 95.8% and 91% respectively in group NR (NS: P=.81). There were no significant differences in morbidity, tracheotomy/nasogastric intubation time, or hospital stay. Positive resection margins (R1) were noted in 38.1% and 16.7% in groups R and NR, respectively (NS: P=.05) without significant impact on 5-year actuarial local control (P=0.78). ConclusionRobotic assistance in transoral lateral oropharyngectomy for T1-2 tonsillar fossa SCC did not significantly impact oncologic or functional outcome.

Multi-Institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiotherapy Using Weekly Cisplatin for Patients with Pelvic Node-Positive Cervical Cancer in East and Southeast Asia

This multi-institutional observational study conducted among 11 Asian countries aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiotherapy using weekly cisplatin for patients with locally advanced cervical cancer in East and Southeast Asia. Uterine cervical cancer is among the most common cancers in East and Southeast Asia, and the mortality rate remains high in these countries because many patients present at a relatively advanced stage. It is necessary to develop new treatment methods for locally advanced cervical cancer suitable for developing countries. The pattern of spread in cervical cancer appears to be orderly, initially involving the low pelvis and then progressing to high pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN). To control occult PALN metastasis, extended-field radiation therapy including the para-aortic region and PLN region may be one of the effective treatments. Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiotherapy consisted of pelvic irradiation (total dose, 50 Gy/25 fractions including central shielding), prophylactic para-aortic regional irradiation (36-40 Gy/20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned Point A dose was 21-28 Gy in 3-4 fractions for high-dose-rate ICBT and 40-41 Gy in 1-2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiotherapy course. A total of 106 patients were enrolled. Of these, 10 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received four or five cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 (21%) of the patients, and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. The results indicated that prophylactic extended-field concurrent chemoradiotherapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Multi-institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiation Therapy Using Weekly Cisplatin for Patients With Pelvic Node-Positive Cervical Cancer in East and Southeast Asia

This multi-institutional observational study conducted among 11 countries in East and Southeast Asia aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with locally advanced cervical cancer. Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course. A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Update in Temporal Bone Resection Outcomes

Surgical outcomes data related to temporal bone malignancy can be challenging to interpret and apply to a specific patient population due to the overall rarity of the disease and the heterogeneity of disease types often studied in aggregate in this anatomic region. Large institutional series are commonly composed of a diverse patient cohort, with numerous pathologic entities studied in aggregate despite known differences in biologic behavior. Our current aim is to provide a review of recent literature on surgical resection of primary, untreated squamous cell carcinoma of the temporal bone and examine associated outcomes. A general overview of temporal bone carcinoma and illustrated, contemporary update of surgical techniques is additionally provided.

Natural history of untreated squamous cell carcinoma of the head and neck.

Natural history of untreated squamous cell carcinoma of the head and neck.

Untreated meningomyelocele and squamous cell carcinoma: a case report and literature review

Background Early closure of the meningocele, meningomyelocele, is essential to prevent complications such as hypothermia, infection in the postnatal period. But for some reasons, it is not always possible to repair early. The possibility of malign transformation should be considered in long-term due to nonhealing ulcers and cerebrospinal fluid (CSF) fistula and frequent infections in an adult patient with meningomyelocele. The possibility of conversion to malignancy in the control of an untreated meningomyelocele patient with (CSF) drainage should be especially kept in mind. Case description A case is described of a malignant transformation at the site of a myelomeningocele in a 22-year-old woman. The lumbosacral region was deformed by a large meningomyelocele 10 cm in diameter, with areas of scar and ulcer. For 7 years prior to this presentation, the lesion was a large fistula in the roof of the open myelomeningocele. She underwent continuous CSF draining. A biopsy was done which revealed it as squamous cell carcinoma. Conclusion Early closure of meningocele, meningomyelocele is essential to prevent complications such as hypothermia, infection in the postnatal period. Also, especially if there is continuous CSF exposure, the possibility of malignant change should be kept in mind in neglected cases presenting in an adult.

HISTOPATHOLOGICAL DIFFERENCES BETWEEN GENDERS IN PATIENTS WITH ORAL SQUAMOUS CELL CARCINOMA

Introduction: Oral cancer ranks fifth among the most frequent malignant tumors in men in Brazil. The incidence of this tumor among women has grown. It is still controversial whether gender can influence the outcome or the prognostic features of the disease. Objectives : To compare the histopathological features of oral squamous cell carcinomas between genders among patients undergoing surgical treatment in an oncological hospital of southern Brazil. Methods: Between 2007 and 2011, 404 patients underwent resection of malignant tumors of the oral cavity in the head and neck department of this institution. A subgroup of 209 previously untreated oral cavity squamous cell carcinoma cases was selected for comparative analysis. Results: In total, 68 participants were women and 141 were men. The tongue was the most common subsite in both genders. Men presented lower mean age and women presented tumors with smaller depth of invasion. Although among women it was observed a trend towards tumors with less aggressive characteristics, no other variable showed statistically significance. Conclusion: Women with oral tumors tend to present more superficial primary tumors and at a later age. Keywords: Oral neoplasms; carcinoma; squamous cell; prognosis

The Outcomes of Surgery and Chemoradiotherapy for Temporal Bone Cancer.

We aimed to evaluate the prognostic factors and efficacy of treatment modalities for patients with temporal bone cancer, and to determine if definitive chemoradiotherapy (CRT) for advanced-stage disease can provide a substitute for highly invasive surgeries. Retrospective case series. Tertiary referral center. Sixty-six patients with previously untreated squamous cell carcinoma of the temporal bone treated with curative intent between April 1997 and March 2015. Surgery alone, radiotherapy (RT) alone, surgery followed by RT or definitive CRT. The overall survival (OS) rate. The 5-year OS rate for each T classification was 100% for T1, 76.2% for T2, 55.6% for T3, and 36.7% for T4. Univariable and multivariable analysis showed that T classification was an independent predictor of the OS rate (hazard ratio 5.66; 95% confidence interval 1.51-27.0; p = 0.015). Analysis by treatment modality revealed that the 5-year OS rate for patients with T1-2 was 100% for surgery and 81.3% for RT alone. The rate for patients with T3-4 was 52.1% for definitive CRT and 55.6% for surgery followed by RT with or without chemotherapy. Patients with T1-2 benefited from surgical intervention without significant morbidity or mortality. Our findings also suggested that definitive CRT might be appropriate as the first-line treatment for T3-4, especially in cases with unresectable tumors.

Ligand–receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma

ABSTRACTThymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine expressed by epithelial cells during allergic inflammation, and activating dendritic cells (DC). Its expression and functional role in cancer remain controversial. We conducted retrospective (n = 89), and prospective studies including patients with untreated primary head and neck squamous cell carcinoma (HNSCC). We found that TSLP was overexpressed by HNSCC tumor cells, and associated with a highly differentiated status. However, no significant difference in overall and recurrence-free survival was found between patients bearing a tumor with high and low TSLP levels, respectively. Surprisingly, there was no significant association between the levels of TSLP expression, and the number of tumor-infiltrating mature DCLAMP+ DC. In order to explain the apparent lack of TSLP-induced DC activation, we performed phenotypic and functional experiments on freshly resected tumors. Tumor-infiltrating immune cells, including DC, did not express the TSLP receptor heterodimer (TSLPR chain, IL-7Ralpha chain). Furthermore, freshly sorted blood CD11c+ DC from healthy donors cultured with tumor-conditioned supernatant exhibited an activated profile, but this was not affected by an anti-TSLP blocking antibody, suggesting a DC activation pathway independent of tumor-derived TSLP. Overall, our results demonstrate that TSLP is overexpressed in HNSCC but its function is hampered by the lack of TSLPR-expressing cells in the tumor microenvironment. Such a dissociated ligand–receptor expression may impact intercellular communication in other immune activation pathways, and tumor types.

Cancer testis antigen SPAG9 is a promising marker for the diagnosis and treatment of lung cancer.

Cancer testis antigen sperm-associated antigen 9 (SPAG9) is highly expressed in many types of cancers. In the present study, to obtain a better understanding of the relevance of SPAG9 in cancer diagnosis and treatment, the expression of SPAG9 mRNA and protein in lung cancer specimens was evaluated by RT-PCR, western blotting and immunohistochemistry. ELISA was used to quantify the SPAG9 autoantibody in the peripheral blood of lung cancer patients. The results showed that the expression of SPAG9 mRNA and protein in the lung cancer tissues was significantly higher than that in the adjacent non-cancerous tissues (P<0.01). The level of the SPAG9 autoantibody in the serum of lung cancer patients was significantly higher than the level in the healthy controls (P<0.001), and the level of the SPAG9 autoantibody in the serum of untreated patients was significantly higher than that in treated patients (P=0.002). SPAG9 IgG antibody levels were significantly lower in treated adenocarcinoma and small cell lung cancer patients than these levels in the untreated patients (P=0.006, P=0.026, respectively), while no statistical difference was found between treated and untreated squamous cell carcinoma patients. Our results suggest that the SPAG9 antibody in serum is a promising marker for the diagnosis of lung cancer, and the level of the humoral immune response to this antigen appears to be related to the type of lung cancer.

頭頸部扁平上皮癌症例に対する3-WeeklyとWeekly CDDP併用化学放射線療法の臨床的検討

頭頸部扁平上皮癌に対し，3週毎のCDDP（100mg/m2または80mg/m2）を同時併用する化学放射線療法（3-Weekly）とCDDP 40mg/m2/週併用の化学放射線療法（Weekly）について後方視的に比較検討する。対象は2007年11月から2015年3月までにシスプラチン併用の化学放射線療法を実施した頭頸部扁平上皮癌患者34例（下咽頭19例，中咽頭11例，喉頭4例）で，3-Weeklyが26例，Weeklyが8例であった。CDDPの平均総投与量は3-Weeklyでは203mg/m2，Weeklyでは212.5mg/m2であり，CDDP200mg/m2以上投与できた割合は3-Weeklyで65％，Weeklyで88％であった。75歳以上の後期高齢者では，3-Weekly群の3人中0人（0％），Weekly群の4人中3人（75％）がCDDP総投与量200mg/m2を超えた。高齢者に対しては，3-WeeklyよりWeekly CDDPの方が，十分量のCDDPを投与できる可能性が示唆された。

Abstract B85: Tertiary lymphoid structures in chemotherapy-treated and untreated lung squamous cell carcinoma patients

Abstract Tertiary lymphoid structures (TLS) form in chronically inflamed tissues and contain organized compartments of T cells, B cells and follicular dendritic cells (FDCs). TLS were first noticed in autoimmune diseases where they support ectopic germinal center (GC) reactions and facilitate the activation and infiltration of immune cells. In cancer B cell and mature DC markers have been used for TLS detection because of their frequent localisation in TLS, and show a significant association with improved survival in several tumor types. Together these studies have driven the interest in TLS as a potential site of anti-tumor immune response activation and/or facilitation of lymphocyte infiltration. Here we aimed to characterise TLS as a microanatomical structure excluding non-organised lymphocytic infiltrates and to determine their prognostic value and association with clinico-pathologic parameters in non-small cell lung cancer patients. We characterised TLS density and presence of GCs in tumor center and periphery using H&amp;E stained whole sections from 4 different tumor regions of 127 surgically resected lung squamous cell carcinoma (SCC) patients with an annotated 5-year follow-up. Intratumoral TLS where observed in 30% of patients, while &amp;gt;95% of cases showed TLS in the tumor periphery. Patients with TLS-rich (n=65) and TLS-poor (n=62) tumour microenvironments could be distinguished. High density and GC positivity of TLS correlated with increased lymphocyte infiltration (Pearson correlation 0.34, p&amp;lt;0.001), but not other clinical parameters. In neo-adjuvant chemotherapy-naïve patients, high density of GC-containing TLS was a significant positive prognosticator for disease free survival independent of pTNM, tumor grade, vascular and pleural invasion, age, gender, or pack years (n=87, multivariate Cox regression p=0.006, hazard ratio=0.365, 95% CI 0.18-0.75). In contrast, prognostic significance was abrogated in patients treated by neo-adjuvant chemotherapy using a doublet of platinum-containing drug with either gemcitabine, taxanes or vinorelbine. We observed that the density of TLS in tumor periphery was not altered in this cohort compared to untreated patients, but the proportion of TLS with active GCs was decreased (Pearson correlation -0.32, p&amp;lt;0.001). Further, when we stratified the neo-adjuvant chemotherapy-naïve patients along adjuvant chemotherapy post-surgery, the prognostic significance was retained only in the adjuvant untreated group (n=55, multivariate Cox regression p=0.001, hazard ratio=0.17, 95% CI 0.06-0.5). This suggests that chemotherapy might affect the quality rather than formation of TLS and disturb their immunostimulatory function. We further investigated, which factors might affect the density of TLS in tumors. Because the chemokines CXCL13, CXCL12 and CCL21 have been shown to induce TLS formation in the lung under inflammatory conditions, we analyzed their expression in tumor samples by immunohistochemistry. Positive pixel algorithm (ImageJ software) was used for the quantification of immunostained tissue sections in central and peripheral tumor areas. We saw that the overexpression of CXCL13 in both, stromal and cancer cells, was associated with increased density of TLS (Student's T test p&amp;lt;0.05), while the expression of CXCL12 and CCL21 did not differ between the TLS-rich and TLS-poor tumor microenvironments. In conclusion, we propose that the deliberate induction of TLS in lung cancer, possibly by CXCL13, may represent a novel immunotherapeutic approach. Thereto, the identification of molecular changes that chemotherapy exerts on the functionality of TLS, and whether this can be reversed, will provide novel ideas for the combination of immunotherapy with chemotherapy and thereby increasing the efficiency of standard treatments. Citation Format: Karina Silina, Alex Soltermann, Holger Moch, Aija Line, Maries van den Broek. Tertiary lymphoid structures in chemotherapy-treated and untreated lung squamous cell carcinoma patients. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B85.

Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma – The ARTSCAN trial

Background and purposeThis report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methodsPatients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1–2, N0 glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1Gy+2Gy per day, 5days/week for 4.5weeks, total dose 68Gy) and conventional fractionation (CF) (2Gy per day, 5days/week for 7weeks, total dose 68Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. ResultsThere was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p=0.75). LRC at 5years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p=0.99). The estimated cancer specific survival (CSS) at 5years was 62.2% (AF) and 63.3% (CF) (p=0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16− tumours. ConclusionThis update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.