non-SCC Patients Research Articles

Prognostic Factors among Patients with Resected Non-Adenocarcinoma of the Lung

Introduction: Few studies have investigated the prognostic factors for non-adenocarcinoma of the lung. We retrospectively evaluated the prognostic factors on the basis of histological type of non-adenocarcinoma of the lung treated by pulmonary resection. Methods: We enrolled 266 patients with non-adenocarcinoma of the lung in this retrospective study: 196 with squamous cell carcinoma (SCC) and 70 with non-SCC. Results: Relapse-free survival (RFS) did not differ significantly between SCC and non-SCC patients (p = 0.33). For SCC patients, RFS differed significantly between patients who underwent wedge resection and non-wedge resection (p < 0.01) and between patients with Clavien-Dindo grade ≥3a and 0–2 postoperative complications (p < 0.01). For non-SCC patients, RFS rates were significantly different in the groups divided at neutrophil-to-lymphocyte ratio = 2.40 (p = 0.02), maximum standardized uptake value (SUVmax) = 8.39 (p < 0.01), between patients with pathological stage (pStage) 0–I and with pStage more than II (p < 0.01). For SCC patients, male sex (p = 0.04), wedge resection (p = 0.01), and Clavien-Dindo grade ≥3a (p = 0.02) were significant factors for RFS in multivariate analysis. For non-SCC patients, neutrophil-to-lymphocyte ratio >2.40 (p < 0.01), SUVmax >8.39 (p = 0.01), and pStage ≥II (p = 0.03) were significant factors for RFS in multivariate analysis. Conclusion: RFS did not differ significantly differently between SCC and non-SCC patients. It is necessary to perform more than segmentectomy and to avoid severe postoperative complications for SCC patients. SUVmax might be an adaptation criterion of adjuvant chemotherapy for patients with non-adenocarcinoma and non-SCC of the lung.

Class II and class III BRAF mutations in patients with advanced non-small cell lung cancer (NSCLC): Clinical characteristics, mutation patterns, and survival outcomes.

e21204 Background: Class II and class III BRAF mutations (i. e., non-V600X) in NSCLC differ from V600E in terms of dimerization and KRAS-dependency. Whereas V600X is effectively targetable by combined BRAF- and MEK-inhibition, no specific targeted approach for non-V600X exists, and a comprehensive description of the patient group is lacking. This retrospective cohort analysis presents clinical and genomic characteristics of a large cohort of patients with advanced BRAF nonV600X mutant lung cancer. Methods: Molecular data of 1411 lung cancer patients staged IIIb/IV and harboring BRAF mutations were linked to hospital registry data in the NGM (Network Genomic Medicine) database. Biospecimens were analyzed using next-generation sequencing (NGS). Results: 721 patients with BRAF non-V600X mutations were identified, of whom 10.5% had been diagnosed with squamous cell carcinoma (SCC) and 89.5% had non-squamous histology. Median age at diagnosis was 66 years (range: 34-81) and the cohort comprised 409 (56.7%) men and 312 (43.3%) women. 301 (41.8%) of the BRAF non-V600X alterations detected in this cohort are “activators” in the MAPK pathway (class II, including G469A/V/R, G464A/E/L/V, K601E/N, L597Q/R/V), while 310 (43.0%) function as “amplifiers” (class III, including mutants such as D594A/G/H/N, G466A/E/V, G469E, N581I/S/T in this cohort). While 21.5 % (155; SCC: 12.3%; non-SCC: 22.9%) of patients did not have any co-occurring mutations (55.6% of SCC and 37.1% of non-SCC patients respectively), TP53 was the most frequent co-mutation, detected in 56.6% (SCC: 74.0%; non-SCC: 53.8%) of patients. 16.4% (118) exhibited a KRAS co-mutation (SCC: 4; non-SCC: 109). A preliminary survival analysis suggests no significant difference in overall survival between these broad classes (HR 0.92, 95%-CI 0.62, 1.36). Conclusions: The study highlights the heterogeneity of patients with BRAF class II and class III regarding histology and co-mutational status, with both classes equally frequent. A more granular investigation of non-V600X alterations and their associated clinical outcomes under different treatment approaches is ongoing.

Non-Squamous Cell Malignancies of the Larynx.

Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied. Retrospective cohort study. Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients. A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001). A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients. 4 Laryngoscope, 132:1771-1777, 2022.

Stereotactic Body Radiotherapy (SBRT) With Biologically Equivalent Dose > 150 Gy is Associated With Improved Local Control in Patients With Squamous but not Non-Squamous Cell Carcinoma of the Lung: A Multi-Institutional Analysis

<h3>Purpose/Objective(s)</h3> Recent studies suggest improved local control (LC) of early-stage non-small cell lung cancer (NSCLC) treated with SBRT regimens with biologically equivalent dose (BED₁₀) > 150 Gy. It is unclear if this association is histology dependent. Multiple groups have shown lower LC rates after SBRT for squamous cell carcinoma (SCC), compared to non-SCC NSCLC. We compared LC between BED_low and BED_high SBRT schemes, stratified by histology. <h3>Materials/Methods</h3> As part of an IRB approved collaborative, we retrospectively analyzed 684 patients with cT1-2, cN0, cM0 NSCLC, treated with definitive SBRT to a minimum BED of 100 Gy at five international centers. Patients were grouped into SCC and non-SCC, then divided into BED_high (BED₁₀ ≥150 Gy) or BED_low (BED10 < 150 Gy) based on prescription dose, and propensity-score matched for age, sex, smoking history, performance status, T-stage, tumor grade and location, mediastinal staging, and receipt of chemotherapy. LC was estimated by Kaplan-Meier. Univariate (UVA) and multivariable analyses (MVA) were used to correlate BED with clinical outcomes. We also compared BED groups based on dose to planning and gross target volumes (PTVmean, GTVmean) to account for plan heterogeneity among institutions. <h3>Results</h3> Of 684 eligible tumors, 457 were non-SCC and 227 SCC. Median follow-up was 30 months. Of non-SCC patients, 262 (57%) were BED_low and 195 (43%) BED_high. Of SCC patients, 144 (63%) were BED_low and 83 (37%) BED_high. BED_high SBRT included those treated with 54 Gy in 3 fractions (54/3). BED_low included 60/5, 50/5, 48/4, or 60/8. Baseline characteristics, including T-stage and max tumor dimension, were similar between BED groups after matching. MVA including T-stage, tumor grade, and tumor location, showed BED_low regimens were associated with higher rates of local failure for SCC (HR 9.8, 95% CI 1.9-25.1, <b>P</b> = 0.007), but not for non-SCC (HR 1.2, 95% CI 0.6-2.5, <b>P</b> = 0.6). Three-year LC rates for BED_low and BED_high were 70% and 97%, respectively for SCC, and 91% and 92%, respectively, for non-SCC. Similarly, there were higher rates of failure with BED_low PTVmean (3 yr LC 94 vs 69%, MVA HR 6.4, 95% CI 1.9-22.2, <b>P</b> = 0.003) and BED_low GTVmean (3 yr LC 87 vs 68%, MVA HR 7.6, 95% CI 2.7-21.6, <i>P</i> = 0.001) in SCC patients. In non-SCC patients, LC was similar between BED groups for PTVmean (3 yr LC 92% vs 93%, MVA HR 1.1, 95% CI 0.5-2.8, <b>P</b> = 0.8) and GTVmean (3 yr LC 94 vs 90%, MVA HR 0.8, 95% CI 0.3-2.6, <b>P</b> = 0.8). There was a trend of worse survival in BED_low SCC patients (MVA HR 1.3, 95% CI 0.9-1.9, <b>P</b> = 0.1), but survival was similar in non-SCC patients (MVA HR 1.02, 95% CI 0.8-1.3, <b>P</b> = 0.9). There were no differences in regional recurrence or distant metastases between BED groups in either histology. <h3>Conclusion</h3> This multi-institutional analysis shows improved LC in early-stage SCC NSCLC treated with SBRT regimens with BED₁₀ > 150 Gy. No difference was observed in LC between BED groups for non-SCC patients. Our results suggest BED_high SBRT should be strongly considered for early-stage non-central SCC NSCLC.

Disease Characteristics and Patterns of Failure by Histologic Type for Patients Treated With Definitive Radiation for Cervical Cancer

To assess differences in disease characteristics at the time of diagnosis and patterns of failure by histologic subtype following definitive therapy for cervical cancer.Patients with cervical cancer who received definitive radiation between 2004 and 2017 at a single institution were identified. Concurrent chemotherapy was given at the discretion of the treating gynecologic oncologist with consideration of performance status and medical comorbidities. Details regarding disease characteristics, treatment parameters, and patient outcomes were collected. Patients were staged according to the 2009 FIGO staging criteria; and, details regarding the presence of clinically positive pelvic or para-aortic lymph nodes were included (currently, considered FIGO IIICI and IIIC2). Patients were divided between squamous (SCC) and non-squamous histologies (non-SCC) for outcome and disease characteristic analysis. Kaplan-Meier (KM) method was used to estimate progression free survival (PFS), distant metastasis free survival (DMFS), and overall survival (OS). A Cox proportional hazards model was utilized to identify if histologic type was associated with patient outcomes.266 patients who received definitive radiation were identified with a median follow up of 34 months. 94% of patients received cisplatin based concurrent chemotherapy. 216 (81%) had squamous cell carcinoma, 36 (14%) had adenocarcinoma, 13 (5%) had adenosquamous carcinoma, and one patient had had a neuroendocrine small cell tumor. Patients with SCC were more likely than those with non-SCC to have involved lymph nodes (50% vs 36%, P = 0.047) and have FIGO Stage II-IVA disease (57% vs 42%, P = 0.016). The KM estimated 5-year PFS (57% vs 64%), DMFS (61% vs 71%), and OS (65% vs 71%) were not significantly different between those with SCC and non-SCC. On multivariable analysis, histologic distinction of SCC or non-SCC was not associated with PFS, DMFS, or OS. Increasing FIGO stage was associated with worse PFS (HR 1.2 per stage increase, 95% CI 1.1-1.3, P = 0.001), DMFS (HR 1.2 per stage increase, 95% CI 1.1-1.3, P = 0.001), and OS (HR 1.2 per stage increase, 95% CI 1.1-1.4, P < 0.0001). The presence of clinically positive para-aortic lymph nodes was also associated with worse PFS (HR 4.3 compared to no nodes, 95% CI 2.5-7.4, P < 0.0001), DMFS (HR 4.8 compared to no nodes, 95% CI 2.7-8.6, P < 0.0001), OS (HR 4.0 compared to no nodes, 95% CI 2.1-7.4, P < 0.0001) CONCLUSION: In a large single institution database, patients with non-SCC cervical cancer were more likely to present with earlier stage disease (FIGO Stage I) and were less likely to have clinically positive lymph nodes. However, despite the earlier presentation of these non-SCC patients, there was no difference in PFS, DMFS, or OS between the groups. Consideration of additional treatments, including variations in systemic therapy, dose escalation, or surgery, should be evaluated for non-SCC histology cervical cancer patients to improve outcomes in the future.D.F. Cousins: None. J. Sanders: None. D.A. Muller: None. K.A. Ward: None. E. Asare: None. B. Libby: None. T.N. Showalter: Research Grant; Varian Medical Systems. board member and committee chair in ABS; American Brachytherapy Society. K. Romano: None.

Temporal trends, tumor characteristics and stage-specific survival in penile non-squamous cell carcinoma vs. squamous cell carcinoma

PurposeTo compare Cancer-specific mortality (CSM) in patients with Squamous cell carcinoma (SCC) vs. non-SCC penile cancer, since survival outcomes may differ between histological subtypes.MethodsWithin the Surveillance, Epidemiology and End Results database (2004–2016), penile cancer patients of all stages were identified. Temporal trend analyses, cumulative incidence and Kaplan–Meier plots, multivariable Cox regression and Fine and Gray competing-risks regression analyses tested for CSM differences between non-SCC vs. SCC penile cancer patients.ResultsOf 4,120 eligible penile cancer patients, 123 (3%) harbored non-SCC vs. 4,027 (97%) SCC. Of all non-SCC patients, 51 (41%) harbored melanomas, 42 (34%) basal cell carcinomas, 10 (8%) adenocarcinomas, eight (6.5%) skin appendage malignancies, six (5%) epithelial cell neoplasms, two (1.5%) neuroendocrine tumors, two (1.5%) lymphomas, two (1.5%) sarcomas. Stage at presentation differed between non-SCC vs. SCC. In temporal trend analyses, non-SCC diagnoses neither decreased nor increased over time (p > 0.05). After stratification according to localized, locally advanced, and metastatic stage, no CSM differences were observed between non-SCC vs. SCC, with 5-year survival rates of 11 vs 11% (p = 0.9) for localized, 33 vs. 37% (p = 0.4) for locally advanced, and 1-year survival rates of 37 vs. 53% (p = 0.9) for metastatic penile cancer, respectively. After propensity score matching for patient and tumor characteristics and additional multivariable adjustment, no CSM differences between non-SCC vs. SCC were observed.ConclusionNon-SCC penile cancer is rare. Although exceptions exist, on average, non-SCC penile cancer has comparable CSM as SCC penile cancer patients, after stratification for localized, locally invasive, and metastatic disease.

Outcomes of Pulmonary Arterial Hypertension Are Improved in a Specialty Care Center

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressures and is managed by vasodilator therapies. Current guidelines encourage PAH management in specialty care centers (SCCs), but evidence is sparse regarding improvement in clinical outcomes and correlation to vasodilator use with referral. Is PAH management at SCCs associated with improved clinical outcomes? A single-center, retrospective study was performed at the University of Pittsburgh Medical Center (UPMC; overseeing 40 hospitals). Patients with PAH were identified between 2008 and 2018 and classified into an SCC or non-SCC cohort. Cox proportional hazard modeling was done to compare for all-cause mortality, as was negative binomial regression modeling for hospitalizations. Vasodilator therapy was included to adjust outcomes. Of 580 patients with PAH at UPMC, 455 (78%) were treated at the SCC, comprising a younger (58.8 vs64.8 years; P< .001) and more often female (68.4%vs51.2%; P< .001) population with more comorbidities without differences in race or income. SCC patients demonstrated improved survival (hazard ratio, 0.68; P= .012) and fewer hospitalizations (incidence ratio, 0.54; P< .001), and provided more frequent disease monitoring. Early patient referral to SCC (< 6months from time of diagnosis) was associated with improved outcomes compared with non-SCC patients. SCC patients were more frequently prescribed vasodilators (P< .001) and carried more diagnostic PAH coding (P< .001). Vasodilators were associated with improved outcomes irrespective of location but without statistical significance when comparing between locations (P > .05). The UPMC SCC demonstrated improved outcomes in mortality and hospitalizations. The SCC benefit was multifactorial, with more frequent vasodilator therapy and disease monitoring. These findings provide robust evidence for early and regular referral of patients with PAH to SCCs.

Nonsquamous cell laryngeal cancers: Incidence, demographics, care patterns, and effect of surgery

To analyze the incidence and clinical profile of nonsquamous cell (non-SCC) laryngeal carcinomas and to analyze the effect of surgery on survival. A retrospective analysis of the National Cancer Database (2004-2014). Adult patients with non-SCC laryngeal cancers were divided into six major histological subtypes. A descriptive clinical profile was obtained for non-SCC patients, and multivariate regressions were performed to analyze the effect of surgery on survival within the non-SCC cohort. We identified 878 cases of non-SCC laryngeal cancers, representing 1.02% of all malignant laryngeal cancers. Neuroendocrine tumors and bone/cartilage sarcomas made up the largest groups (37.02% and 32.35%, respectively). Metastasis (M) was higher in neuroendocrine tumors, representing 19.1% of those with known clinical M stages. Of those treated, the majority of patients with bone/cartilage sarcomas (80.9%) and minor salivary gland tumors (82.6%) received surgery as part of their treatment. Survival varied significantly based upon histology, with bone/cartilage sarcomas having the highest 5-year survival at 90.4%, and neuroendocrine tumors exhibiting the poorest 5-year survival at 25.7%. Multivariate analyses found surgery to be significantly associated with improved survival (hazard ratio: 0.679; 95% confidence interval: 0.472-0.976; P = 0.036). The specific surgical method (i.e., local excision vs. partial vs. total laryngectomy) did not have any effect on survival. Approximately 1% of all malignant laryngeal cancers are non-SCC in origin. At presentation, neuroendocrine tumors have the highest rate of distant metastasis and have the worst prognosis of the non-SCC cancers. Most non-SCC patients received surgery as part of their treatment regimen. NA. Laryngoscope, 129:2496-2505, 2019.

Surgical and Oncologic Outcomes of Radical Abdominal Trachelectomy Versus Hysterectomy for Stage IA2-IB1 Cervical Cancer

To compare the surgical and oncologic outcomes between abdominal radical trachelectomy (ART) and radical hysterectomy (RH) for stage IA2-IB1 cervical cancer. A retrospective cohort study (Canadian Task Force classification II-2). Shandong Cancer Hospital, Shandong, China. Three hundred twenty-nine patients with IA2-IB1 cervical cancer. All patients underwent ART or RH. All patients were divided into ART (n = 143) and RH (n = 186) groups according to the surgical approach. Additionally, oncologic and fertility outcomes were compared for different tumor pathologies and sizes in ART patients. The ART group had similar case characteristics as the RH group, except that the ART group had a longer surgical time. During a similar follow-up period, there were 4 (2.9%) recurrences and 3 (2.2%) patients who died from recurrence in the ART group compared with 8 (4.6%) recurrences and 4 (2.3%) patients who died from recurrence in the RH group (p = .444 and p = .999, respectively). In the ART group, squamous cell carcinoma (SCC) patients had a 5-year overall survival and pregnancy rate similar to those of non-SCC patients (98.1% vs 96.8%, p = .999; 33.3% vs 26.7%, p = .873), and patients with tumors ≤2 cm and 2 to 4 cm experienced a similar 5-year overall survival rate (97.0% vs 98.6%, p = .999), except patients with tumors ≤2 cm had a higher pregnancy rate (45.2% vs 17.2%, p = .020). ART seems to have similar surgical and oncologic outcomes to RH, except ART has a longer surgical time. Both non-SCC patients and stage IA2-IB1 patients with 2- to 4-cm tumors can undergo ART safely. Patients with tumors ≤2 cm have a higher pregnancy rate than patients with 2- to 4-cm tumors.

Immunohistochemical assays incorporating SP142 and 22C3 monoclonal antibodies for detection of PD-L1 expression in NSCLC patients with known status of EGFR and ALK genes.

Different immunohistochemical (IHC) assays were approved for PD-L1 expression examination on tumor cells in qualification to immune-checkpoint inhibitors therapy in NSCLC patients. These assays have some similarities, but also very serious differences. We assessed 2 IHC tests for PD-L1 expression evaluation in NSCLC tumors with different pathological diagnoses and genetic abnormalities.We enrolled 48 NSCLC patients (median age: 65 years) with known status of EGFR and ALK genes. We compared the effectiveness of PD-L1 expression examination of two IHC assays with 22C3 (Dako) and SP142 antibodies (Ventana). IHC tests were performed in resected tissue samples and in cellblocks from bronchoscopy biopsies (formalin-fixed paraffin-embedded). IHC staining was carried out on Dako Autostainer Link 48 and Ventana Benchmark GX.The percentage of tumors with PD-L1 expression of ≥5% and ≥50% on tumor cells was significantly (p<0.05) higher in assay with 22C3 (66.7% and 45.8%) than with SP142 antibody (39.6% and 22.9%). The median percentage of tumor cells with PD-L1 expression was significantly (p<0.0001) higher in test with 22C3 than with SP142 antibody. Percentage of squamous cell carcinoma (SCC) patients with PD-L1 expression was significantly higher than of non-SCC patients. Large group of patients without PD-L1 expression on tumor cells was identified among patients with common EGFR mutations and ALK rearrangement.Our results support that the highest PD-L1 expression on tumor cells occurs in SCC patients and in adenocarcinoma patients without common, druggable genetic abnormalities. The above mentioned results were clearly visible in IHC assay with 22C3 (strong cell staining).

P2.03b-053 Role of KRAS Mutation Status in NSCLC Patients Treated on SWOG S0819, a Phase III Trial of Chemotherapy with or without Cetuximab: Topic: Biomarkers

The S0819 phase III study of chemotherapy and bevacizumab (by patient/physician choice) with or without cetuximab in NSCLC showed no benefit from the addition of cetuximab, either overall or within the EGFR FISH-positive subset. Secondary analysis suggested an overall survival benefit in EGFR FISH-positive squamous cell carcinoma (SCC) (Herbst WCLC 2015, Hirsch ASCO 2016). In colorectal cancer (CRC), benefit from EGFR monoclonal antibodies such as cetuximab is limited to patients with RAS wild type (WT) tumors; however, in NSCLC, previous studies have not been sufficiently powered to make this determination. We prospectively incorporated KRAS mutation testing in S0819 to determine whether it predicts cetuximab efficacy. Since KRAS mutations are rare in SCC, we focused this analysis on nonSCC. KRAS mutation status was determined using the Therascreen KRAS test (Qiagen), conducted in a CLIA-certified diagnostic laboratory at the UC Davis Comprehensive Cancer Center. This test is FDA-approved for KRAS diagnostics in metastatic CRC, and identifies 6 mutations at codon 12 (G12A,D,R,C,S,V) plus G13D. KRAS mutation status was available for 448 nonSCC patients, and mutations were identified in 150 cases (33%). Amino acid substitutions matched the expected distribution for a NSCLC population, with 52% harboring G12C and 17% with G12V. No significant differences were observed between KRAS-mut and WT populations for PFS (HR=1.15 (0.94-1.42); p=0.18) or OS HR=1.10 (0.89-1.37); p=0.39). Furthermore, no differences in outcomes between arms were observed based on KRAS mutation status (Table). The KRAS WT, EGFR FISH+ molecular subset (hypothetically the most likely subgroup to benefit from cetuximab) showed no statistical differences in outcomes between arms. Determination of KRAS mutation status did not identify a subgroup of nonSCC patients with differential outcome from addition of cetuximab to front-line chemotherapy. In contrast to CRC, cetuximab does not appear to confer benefit to patients with KRAS-WT nonSCC NSCLC.

Comparison of Re-irradiation Outcomes for Charged Particle Radiotherapy and Robotic Stereotactic Radiotherapy Using CyberKnife for Recurrent Head and Neck Cancers: A Multi-institutional Matched-cohort Analysis

To compare survival outcomes for charged particle radiotherapy (CP) and stereotactic body radiotherapy using CyberKnife (CK) in patients who had undergone re-irradiation for head and neck cancers. We conducted a retrospective multi-institutional matched-cohort analysis on 25 patients treated with CP and 25 matched patients treated with CK according to three prognostic factors (nasopharyngeal cancer or not, interval between initial radiotherapy and re-irradiation, and planning target volume). CP was used more often to treat non-squamous cell cancer ((non-SCC): 52% vs. 0%) with a higher prescribed dose (median=57.6 Gy(RBE)/16 fractions) than CK (32 Gy/5 fractions). The local control rate (LC) for patients treated with CP was 71.2% at 1 year and that for patients treated with CK was 63.8% (p=0.24). The 1-year overall survival (OS) rates were 67.1% for CP and 36.3% for CK (p=0.0002), respectively. Non-SCC patients showed better OS rates at 1 year than SCC patients. In the SCC sub-group analysis, the 1-year LC, OS rates were 65%, 58.3% in the CP group and 64%, 36.3% in the CK group (p=0.81, p=0.02), respectively. A total of 16 patients (32%) experienced grade 3 or worse toxicities (24% in CK and 40% in CP, p=0.36), including six grade 5 toxicities. CP produced higher survival rates than CK, treated more non-SCC patients and used a higher prescribed dose. On the other hand, severe toxicities occurred in both groups, which, however, require further investigation.

IMRT/VMAT for malignancies in the head-and-neck region : Outcome in patients aged80.

ObjectiveElderly patients with malignant head-and-neck tumors (HNT) often pose a therapeutic challenge. They frequently have significant comorbidities which may influence their ability to tolerate tumor-specific therapies. Our aim was to investigate the outcome of patients aged 80+ years undergoing curative intent intensity- or volume-modulated radiation therapy (IMRT/VMAT).MethodsWe retrospectively reviewed our HNT patients aged 80+ treated with curative IMRT/VMAT from December 2003 to November 2015. Overall survival (OS), disease-free survival (DFS), local control (LC), and treatment tolerance were assessed. Outcome results were compared with that of a younger HNT patient cohort from our hospital.ResultsA total of 140 consecutive patients were included (65 postoperative, 75 definitive). Mean/median age at treatment start was 84.8/84.1 years (range 80–96 years). Mean/median follow-up time was 25/16 months (range 2–92 months). Of the 140 patients, 80 were alive with no evidence of disease when last seen, 28 had died due to the cancer, 12 remained alive with disease, the remaining 20 died intercurrently. Systemic concomitant therapy was administered in 7 %. Late grade 3–4 toxicity was observed in 2 %. All patients completed treatment. Hospitalization and feeding tube rates were 26 % and 11 %, respectively. The 2‑/3-year LC, DFS, and OS rates for the entire cohort were 81/80 %, 69/63 %, and 68/66 %, respectively. Squamous cell carcinoma (SCC) patients showed an inferior 3-year OS rate as compared to non-SCC patients (62 % vs 77 %, p = 0.0002), while LC and DFS did not differ. Patients undergoing postoperative radiation attained a higher OS compared to the definitively irradiated subgroup with 74 vs. 60 % at 3 years (p = 0.01); however, DFS rates were similar for both groups (68 vs. 61 %, p = 0.15). Corresponding rates for >1400 HNT patients <80 years treated during the same time interval were 81/80 %, 69/67 %, and 77/72 %, respectively.ConclusionsTreatment tolerance in our patients aged 80+ was high. These results suggest that elderly HNT patients should not be denied potentially curative treatment strategies.

Boron neutron capture therapy in non-SCC patients with intractable head and neck malignancies who have no other treatment options.

e17507Background: Boron neutron capture therapy (BNCT) is a targeted type of radiotherapy that has a number of significant advantages over conventional external beam photon irradiation, especially ...

Controlling distant metastasis and surgical treatment are crucial for improving clinical outcome in uncommon head and neck malignancies, such as non-squamous cell carcinoma.

The objective of this study was to elucidate the clinical characteristics of uncommon head and neck malignancies, such as non-squamous cell carcinoma (SCC), in order to improve patient outcomes. A total of 463 head and neck malignancies were retrospectively analyzed, with 43 cases (9.3%) diagnosed as non-SCC. The overall survival rate of patients with adenoid cystic carcinoma was significantly worse compared to that of patients with SCC. The 5-year survival rates were <50% for patients with malignant melanoma, adenocarcinoma, small-cell carcinoma and sarcomas. Distant metastasis to the lung was frequently observed in cases with a poor outcome. Non-SCC malignancies treated without surgery were associated with a worse outcome. Some non-SCC patients had a poor prognosis and distant metastasis was associated with an unsatisfactory outcome. Timely treatment and control of distant metastasis are essential and surgical treatment should be prioritized in non-SCC cases to improve patient outcomes.

Abstract 4328: Broadband diffuse reflectance spectroscopy noninvasively detected in vivo hemoglobin concentration and oxygen saturation of normal and malignant oral tissues

Abstract Tumor physiological properties play an important role in cancer diagnosis and treatments. Diffuse reflectance spectroscopy has emerged as an important technique that provides several unique measurable parameters for characterization of a wide variety of tissue samples. By illuminating visible-NIR light at one location of tissue surface (source position) and collecting diffused light at another location (detection position) using optical fibers, we are able to access tissue physiological properties including total hemoglobin concentration (THC) and oxygen saturation (StO2). The depth of the measured tissue is determined by the source-detection separation that is approximately one third to one half of the separation. In oral cancers, close associations were found between tumor progression and tumor angiogenesis and hypoxia through the molecular markers. However, the prognostic and therapeutic value of these markers is not clearly known. The first goal of this study is to demonstrate the visibility of monitoring tissue THC and StO2 of normal and squamous cell carcinoma (SCC), which represent ∼95% of oral malignancies. Our 2nd goal is to compare these optical measured physiological properties to molecular markers from the same tissues. We have collected data from 25 SCC and 24 non-SCC (hyperplasia and dysplasia) patients at the department of dentistry, Taichung Veterans General Hospital. Adjacent normal sites were measured optically as well in the same patient. Optical measurements were analyzed by employing a physical model of light transport inside the tissue to extract THC and StO2. From all measurements, the THC and StO2 have a range of 25 and 229 uM and of 25 and 100%, respectively, while the source-detection separation at 4 mm (the detection depth 1.3 to 2 mm) was used. SCC did not show significant different THC and StO2 (mean±STD: 117±48 uM and 72±19%, respectively) from the normal site of the same patient (115±61 uM and 69±19%, respectively) and the non-SCC tissues (117±49 uM and 68±22%). While shorter source-detection separation was used (the detection depth was less than 1mm), the results from 7 SCC and 7 non-SCC patients show higher THC than normal and non-SCC tissues (233 uM versus 182 uM). Well oxygenated tissue layers were detected in both SCC, non-SCC, and normal sites with a range of 92 and 100%. The data indicated that both normal and malignant oral tissues are well oxygenated. Increased THC in SCC sites was observed only when the surface layer at the depth less than 1 mm was compared. Further analysis from all tissue sites will be performed to confirm this finding. The results of molecular markers will be compared with these optical measurements and the prognostic and therapeutic value of these markers will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4328.

Clinical usage of the squamous cell carcinoma antigen in patients with penile cancer

We present our initial experience with the use of the squamous cell carcinoma (SCC) antigen (SCCAg) in 16 men with penile SCC (SCC group), in four men with condyloma acuminatum (benign group), and in 32 blood donors (control group). The SCCAg levels were measured at presentation and every 6 months (upper limit was 2 ng/mL). The mean follow-up time was 4 years. All non-SCC patients had normal SSCAg serum levels in contrast with the SCC patients. The presence of nodal and/or distant metastases resulted in statistically significant higher SCCAg levels, both at presentation and during the follow-up. In patients undergoing lymph node dissection with elevated SCCAg levels prior to the procedure, there was a statistically significant decrease of the SCCAg levels after the operation. The SCCAg level could be a serum marker that holds promise for clinical use in penile SCC. Sequential monitoring of SCCAg level might indicate developing of nodal and/or distant metastases and could be useful in following the response to treatment.

Clinical implication of cyclin B1 in non-small cell lung cancer

Cyclin B1 plays an important role in the mitotic cycle, in which it regulates the G2-M transition, and has been suggested to play a role in development and progression of various cancers. The present study was undertaken in order to clarify the role of the cell cycle regulator cyclin B1 in non-small cell carcinoma (NSCLC). We retrospectively investigated 174 patients with NSCLC who previously underwent complete resection. There were two study groups: the squamous cell carcinoma (SCC) group (n=62); and the non-SCC group (n=112). Expression of cyclin B1 in cancer cells was analyzed immunohistochemically. The rate of cyclin B1 positivity in cancer cells ranged from 0% to 56.5% (average 10.9%). Seventy-four cases (42.5%) were designated as cyclin B1 positive in the present study. Cyclin B1 expression was observed more frequently in SCC cases than in non-SCC cases. In SCC, cyclin B1 expression demonstrated significant correlation with gender (p<0.01) and histological type (p<0.01). In non-SCC, only gender was correlated with cyclin B1 expression. Five-year survival rates for cyclin B1-positive and cyclin B1-negative cases were 45.8 and 57.9%, and 10-year survival rates were 39.3 and 51.4%, respectively. Patients with positive cyclin B1 staining showed a lower survival rate than those with negative staining (p=0.11). The prognostic value in SCC cases was p=0.48. In non-SCC cases, the survival rate of non-SCC patients who were positive for cyclin B1 was significantly lower than that of patients who were negative (p<0.01). Using multivariate analysis, tumor size (p=0.037) and N factor (p=0.026) were found to be independent prognostic parameters. Cyclin B1 expression was not an independent prognostic factor in the present series. These data suggest that elevated levels of cyclin B1 expression may be an indicator of poor prognosis in NSCLC, particularly in non-SCC.

Clonal chromosome aberrations accumulate with age in upper aerodigestive tract mucosa

Short-term cultured non-neoplastic upper aerodigestive tract (UAT) mucosa samples from 36 patients with squamous cell carcinoma of the head and neck (SCC) and 53 patients with benign UAT disorders were cytogenetically analyzed. The cell cultures were divided into two series: in series A, cells were cultured in a medium stimulating outgrowth of mesenchymal cells; whereas the cultured cells in series B were of epithelial morphology. Series A was further subdivided into three different age groups (≤15 years, 16–59 years, and ≥60 years) of non-SCC patients and one SCC group. Series B was composed of two groups; one with and one without SCC. Among the non-SCC patients in series A, there was an increase with age in the frequency of cells/sample with numerical and structural chromosomal changes as well as in the incidence of clonal chromosomal aberrations. No differences could, however, be detected between cancer patients and age-matched controls. In series B, the frequency of cells/sample with numerical changes and the incidence of clonal numerical aberrations were significantly higher among SCC patients. Three main conclusions could be drawn. First, the frequencies of clonal and non-clonal chromosome aberrations in UAT mucosa were age dependent. Second, the cytogenetic support for the validity of the field cancerization hypothesis was restricted to increased levels of numerical chromosome changes in epithelial cell cultures from cancer patients. Third, clonal chromosome aberrations, including autosomal and sex chromosome aneuploidies as well as structural rearrangements, are not restricted to neoplastic mucosal cells.

Clonal chromosome aberrations accumulate with age in upper aerodigestive tract mucosa

Abstract Short-term cultured non-neoplastic upper aerodigestive tract (UAT) mucosa samples from 36 patients with squamous cell carcinoma of the head and neck (SCC) and 53 patients with benign UAT disorders were cytogenetically analyzed. The cell cultures were divided into two series: in series A, cells were cultured in a medium stimulating outgrowth of mesenchymal cells; whereas the cultured cells in series B were of epithelial morphology. Series A was further subdivided into three different age groups (≤15 years, 16–59 years, and ≥60 years) of non-SCC patients and one SCC group. Series B was composed of two groups; one with and one without SCC. Among the non-SCC patients in series A, there was an increase with age in the frequency of cells/sample with numerical and structural chromosomal changes as well as in the incidence of clonal chromosomal aberrations. No differences could, however, be detected between cancer patients and age-matched controls. In series B, the frequency of cells/sample with numerical changes and the incidence of clonal numerical aberrations were significantly higher among SCC patients. Three main conclusions could be drawn. First, the frequencies of clonal and non-clonal chromosome aberrations in UAT mucosa were age dependent. Second, the cytogenetic support for the validity of the field cancerization hypothesis was restricted to increased levels of numerical chromosome changes in epithelial cell cultures from cancer patients. Third, clonal chromosome aberrations, including autosomal and sex chromosome aneuploidies as well as structural rearrangements, are not restricted to neoplastic mucosal cells.