Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces significant modifications from the prior seventh edition. This article details several of the most significant modifications, and the rationale for the revisions, to alert the reader to evolution of the field. The most significant update creates a separate staging algorithm for high-risk human papillomavirus-associated cancer of the oropharynx, distinguishing it from oropharyngeal cancer with other causes. Other modifications include: the reorganizing of skin cancer (other than melanoma and Merkel cell carcinoma) from a general chapter for the entire body to a head and neck-specific cutaneous malignancies chapter; division of cancer of the pharynx into 3 separate chapters; changes to the tumor (T) categories for oral cavity, skin, and nasopharynx; and the addition of extranodal cancer extension to lymph node category (N) in all but the viral-related cancers and mucosal melanoma. The Head and Neck Task Force worked with colleagues around the world to derive a staging system that reflects ongoing changes in head and neck oncology; it remains user friendly and consistent with the traditional tumor, lymph node, metastasis (TNM) staging paradigm. CA Cancer J Clin 2017;67:122-137. © 2017 American Cancer Society.

Identification of prognostic molecular biomarkers in 157 HPV-positive and HPV-negative squamous cell carcinomas of the oropharynx.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing due to high-risk HPV infection. We explored the significance of genetic alterations in HPV-positive (HPV-P) and HPV-negative (HPV-N) OPSCC patients on long-term outcome. A total of 157 cases of primary resected OPSCC diagnosed from 1978 to 2005 were subjected to a targeted exome sequencing by MSK-IMPACT™ interrogating somatic mutations in 410 cancer-related genes. Mutational profiles were correlated to recurrence and survival outcomes. OPSCC included 47% HPV-positive (HPV-P) and 53% HPV-negative (HPV-N) tumors arising in the base of tongue (BOT, 43%), palatine tonsil (30%) and soft palate (SP, 27%). HPV negative status, SP location and smoking were associated with poorer outcome. Poorer overall survival was found in NOTCH1-mutated HPV-P (p = 0.039), and in SOX2-amplified HPV-N cases (p = 0.036). Chromosomal arm gains in 8p and 8q, and 16q loss were more common in HPV-P (p = 0.005, 0.04 and 0.01, respectively), while 9p, 18q and 21q losses were more frequent in HPV-N OPSCC (p = 0.006, 0.002 and 0.01, respectively). Novel, potentially functional JAK3, MYC and EP300 intragenic deletions were found in HPV-P, and FOXP1, CDKN2A, CCND1 and RUNX1 intragenic deletions and one FGFR3 inversion were detected in HPV-N tumors. HPV-N/TP53-wild-type OPSCC harbored recurrent mutations in NOTCH1/3/4 (39%), PIK3CA, FAT1 and TERT. In comparison to their oral and laryngeal counterparts, HPV-N OPSCC were genetically distinct. In OPSCC, HPV status, tumor subsite and smoking determine outcome. Risk-stratification can be further refined based on the mutational signature, namely, NOTCH1 and SOX2 mutation status.

Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus.

Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC-SCC). Many new cases of OC-SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC-SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV-negative nonsmoker OC-SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the periodontal pathogens Fusobacterium, Prevotella, Alloprevotella were enriched while commensal Streptococcus depleted in OC-SCC. Based on the four genera plus a marker genus Veillonella for PML, we classified the oral microbiome into two types. Gene/pathway analysis revealed a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2 and 4 along the controls→PML → OC-SCC progression sequence. Our findings suggest an association between periodontal pathogens and OC-SCC in non smoking HPV negative patients.

Minor salivary gland tumors of the head and neck-Memorial Sloan Kettering experience: Incidence and outcomes by site and histological type.

BACKGROUND: Minor salivary gland carcinomas of the head and neck are rare cancers with variable clinical behavior. This study explored the incidence, pathology, clinical behavior, and factors predictive of outcomes in a large cohort of patients treated at Memorial Sloan Kettering Cancer Center over a 30-year period (1985-2015). METHODS: Clinical, pathological, treatment, and outcome data were collected. Unadjusted and adjusted hazard ratios for each variable were calculated with univariate and multivariable Cox regression for survival and recurrence outcomes. RESULTS: Four hundred fifty patients were included: 55% were female, 56% were younger than 60 years, and the median follow-up was 74 months (range, 1-364 months). The most common site was the oral cavity with 305 tumors (68%), which was followed by the oropharynx with 96 (21%), the sinonasal cavity with 38 (8%), the trachea with 7 (2%), and the larynx with 4 (1%). The most common histological types were mucoepidermoid carcinoma (180 tumors [40%]), adenoid cystic carcinoma (141 tumors [31%]), and polymorphous low-grade adenocarcinoma (54 tumors [12%]). The 5-year predicted overall survival rate was 86%, and the disease-specific survival rate was 94% at 5 years. Pathology and tumor stage were significant variables on multivariate analysis for overall survival, disease-specific survival, recurrence-free survival, local recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival. CONCLUSIONS: American Joint Committee on Cancer stage and pathology were the most predictive variables across all outcomes. Tumor site, postoperative radiotherapy, and margin status were not statistically significant variables after tumor stage and pathology were controlled for in most outcomes.

Elective neck dissection (END) and cN0 hard palate and upper gingival cancers: A National Cancer Database analysis of factors predictive of END and impact on survival.

BACKGROUND AND OBJECTIVES: The reported risk of nodal metastasis in hard palate and upper gingival squamous cell carcinoma (SCC) has been inconsistent with inadequate consensus regarding the utility of neck dissection in the clinically negative (cN0) neck. MATERIALS AND METHODS: Using the National Cancer Database, cN0 patients diagnosed with SCC of the head and neck with the subsites of the hard palate and upper gingiva were identified from 2004 to 2014. RESULTS: A total of 1830 patients were identified, and END was performed on 422 patients with cN0 tumors. Pathologically positive nodes occurred in 14% (59/422) of patients in this cohort. Higher tumor stage, academic hospital type, and large hospital volume (>28 cancer-specific cases/year) were associated with a higher likelihood of END both in univariate and multivariate analyses (P < .05). Patients >80 years of age were less likely to receive END on multivariate analysis (OR 0.52, 0.32-0.84). No variables, including advanced T stage, predicted occult metastases. Cox proportional hazards regression analysis showed that patients who underwent END demonstrated improved OS over an 11-year period (hazard ratio 0.75, P = .002). On subgroup analysis, this improvement was significant in patients with both stage T1 and T4 tumors. CONCLUSIONS: Tumor stage, hospital type, and hospital volume were associated with higher rates of END for patients with cN0 hard palate SCC and after controlling for clinical factors, END was associated with improved overall survival.

Feasibility of a Video-Mosaicking Approach to Extend the Field-of-View For Reflectance Confocal Microscopy in the Oral Cavity In Vivo.

BACKGROUND: Reflectance confocal microscopy (RCM) is a developing approach for noninvasive detection of oral lesions with label-free contrast and cellular-level resolution. For access into the oral cavity, confocal microscopes are being configured with small-diameter telescopic probes and small objective lenses. However, a small probe and objective lens allows for a rather small field-of-view relative to the large areas of tissue that must be examined for diagnosis. To extend the field-of-view for intraoral RCM imaging, we are investigating a video-mosaicking approach. METHODS: A relay telescope and objective lens were adapted to an existing confocal microscope for access into the oral cavity. Imaging was performed using metal three-dimensional-printed objective lens front-end caps with coverslip windows to contact and stabilize the tissue and set depth. Four healthy volunteers (normal oral mucosa), one patient (with an amalgam tattoo) in a clinical setting, and 20 anesthetized patients (with oral squamous cell carcinoma [OSCC]) in a surgical setting were imaged. Instead of the usual still RCM images, videos were recorded and then processed into video-mosaics. Thirty video-mosaics were read and qualitatively assessed by an expert reader of RCM images of the oral mucosa. RESULTS: Whereas the objective lens' native field-of-view is 0.75 mm × 0.75 mm, the video-mosaics display larger areas, ranging from 2 mm × 2 mm to 4 mm × 2 mm, with resolution, morphologic detail, and image quality that is preserved relative to that observed in the original videos (individual images). Video-mosaics in healthy volunteers' and the patients' images showed cellular morphologic patterns in the lower epithelium and at the epithelial junction, and connective tissue along with capillary loops and blood flow in the deeper lamina propria. In OSCC, tumor nests could be observed along with normal looking mucosa in margin areas. CONCLUSIONS: Video-mosaicking is a reasonably quick and efficient approach for extending the field-of-view of RCM imaging, which can, to some extent, overcome the inherent limitation of an intraoral probe's small field-of-view. Reading video-mosaics can mimic the procedure for examining pathology: initial visualization of the spatial cellular and morphologic patterns of the tumor and the spread of tumor margins over larger areas of the lesion, followed by digitally zooming (magnifying) for closer inspection of suspicious areas. However, faster processing of videos into video-mosaics will be necessary, to allow examination of video-mosaics in real-time at the bedside. Lasers Surg. Med. 51:439-451, 2019. © 2019 Wiley Periodicals, Inc.

Factors associated with a primary surgical approach for sinonasal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Primary surgery is the preferred treatment of T1-T4a sinonasal squamous cell carcinoma (SNSCC). METHODS: Patients with SNSCC in the National Cancer Data Base (NCDB) were analyzed. Factors that contributed to selecting primary surgical treatment were examined. Overall survival (OS) in surgical patients was analyzed. RESULTS: Four-thousand seven hundred and seventy patients with SNSCC were included. In T1-T4a tumors, lymph node metastases, maxillary sinus location, and treatment at high-volume centers were associated with selecting primary surgery. When primary surgery was utilized, tumor factors and positive margin guided worse OS. Adjuvant therapy improved OS in positive margin resection and advanced T stage cases. CONCLUSIONS: Tumor and non-tumor factors are associated with selecting surgery for the treatment of SNSCC. When surgery is selected, tumor factors drive OS. Negative margin resection should be the goal of a primary surgical approach. When a positive margin resection ensues, adjuvant therapy may improve OS.

Prognostic value of FDG-PET prior to autologous stem cell transplantation for relapsed and refractory diffuse large B-cell lymphoma.

High-dose chemotherapy (HDT) plus autologous stem cell transplantation (ASCT) is the standard of care for chemosensitive relapsed and refractory diffuse large B-cell lymphoma (rel/ref DLBCL). Interim restaging with functional imaging by positron emission tomography using (18)F-deoxyglucose (FDG-PET) has not been established after salvage chemotherapy (ST) and before HDT-ASCT by modern criteria. Herein, we evaluated 129 patients with rel/ref DLBCL proceeding to HDT-ASCT, with ST response assessment by FDG-PET according to the contemporary Deauville 5-point scale. At 3 years, patients achieving a Deauville response of 1 to 3 to ST experienced superior progression-free survival (PFS) and overall survival (OS) rates of 77% and 86%, respectively, compared with patients achieving Deauville 4 (49% and 54%, respectively) (P < .001). No other pre-HDT-ASCT risk factors significantly impacted PFS or OS. Despite achieving remission to ST, patients with Deauville 4 should be the focus of risk-adapted investigational therapies.

Management and outcome of clinically evident neck recurrence in patients with papillary thyroid cancer.

BACKGROUND: The aim of this study was to report our incidence of clinically evident neck recurrence, salvage neck management and subsequent outcomes in patients with papillary thyroid cancer. This is important to know so that patients with thyroid cancer can be properly counselled about the implications of recurrent disease and subsequent outcome. METHODS: An institutional database of 3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed. Patients with nonpapillary histology and gross residual disease and those with distant metastases at presentation or distant metastases prior to nodal recurrence were excluded from the study. Of these, 99 (3.0%) patients developed clinically evident nodal recurrence. Details of recurrence and subsequent therapy were recorded for each patient. Subsequent disease-specific survival (sDSS), distant recurrence-free survival (sDRFS) and nodal recurrence-free survival (sNRFS) were determined from the date of first nodal recurrence using the Kaplan-Meier method. RESULTS: Of the 99 patients, 59% were female and 41% male. The median age was 41 years (range 5-91). The majority of patients had pT3/4 primary tumours (63%) and were pN+ (78%) at initial presentation. The median time to clinically evident nodal recurrence was 28 months (range: 3-264). Nodal recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74 (75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were 89.2% and 93.7%, respectively. CONCLUSION: In our series, isolated clinically evident nodal recurrence occurred in 3.0% of patients. Such patients are successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5 years.

The potential benefit of allogeneic over autologous transplantation in patients with very early relapsed and refractory follicular lymphoma with prior remission duration of ≤12 months.

Early relapsed or refractory follicular lymphoma (FL) warrants consolidation with transplantation, though graft source modality remains controversial. We analysed the outcomes of 44 patients transplanted with either autologous or allogeneic graft sources in the post-rituximab era. No difference in event-free (EFS) or overall survival (OS) was observed between allogeneic (81% and 81%) and autologous transplantation (64% and 70%) at 3 years. There was a significant difference in EFS between allogeneic and autologous transplantation patients with previous remission duration of ≤12 months (80% and 42% at 3 years, P < 0·015). Very early relapsed FL may warrant consideration of allogeneic over autologous transplantation in the appropriate setting.

Role of RAI in the management of incidental N1a disease in papillary thyroid cancer.

BACKGROUND: Following total thyroidectomy (TT) for papillary thyroid cancer (PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes (LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine (RAI) therapy for this indication alone. The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. METHODS: An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival (RFS). RESULTS: The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion (P = 0·01), LNs >2 mm (P = 0·07) and >2 positive nodes (P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively (P = 0·92). CONCLUSION: There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment.

Definition of bulky disease in early stage Hodgkin lymphoma in computed tomography era: prognostic significance of measurements in the coronal and transverse planes.

Disease bulk is an important prognostic factor in early stage Hodgkin lymphoma, but its definition is unclear in the computed tomography era. This retrospective analysis investigated the prognostic significance of bulky disease measured in transverse and coronal planes on computed tomography imaging. Early stage Hodgkin lymphoma patients (n=185) treated with chemotherapy with or without radiotherapy from 2000-2010 were included. The longest diameter of the largest lymph node mass was measured in transverse and coronal axes on pre-treatment imaging. The optimal cut off for disease bulk was maximal diameter greater than 7 cm measured in either the transverse or coronal plane. Thirty patients with maximal transverse diameter of 7 cm or under were found to have bulk in coronal axis. The 4-year overall survival was 96.5% (CI: 93.3%, 100%) and 4-year relapse-free survival was 86.8% (CI: 81.9%, 92.1%) for all patients. Relapse-free survival at four years for bulky patients was 80.5% (CI: 73%, 88.9%) compared to 94.4% (CI: 89.1%, 100%) for non-bulky; Cox HR 4.21 (CI: 1.43, 12.38) (P=0.004). In bulky patients, relapse-free survival was not impacted in patients treated with chemoradiotherapy; however, it was significantly lower in patients treated with chemotherapy alone. In an independent validation cohort of 38 patients treated with chemotherapy alone, patients with bulky disease had an inferior relapse-free survival [at 4 years, 71.1% (CI: 52.1%, 97%) vs 94.1% (CI: 83.6%, 100%), Cox HR 5.27 (CI: 0.62, 45.16); P=0.09]. Presence of bulky disease on multidimensional computed tomography imaging is a significant prognostic factor in early stage Hodgkin lymphoma. Coronal reformations may be included for routine Hodgkin lymphoma staging evaluation. In future, our definition of disease bulk may be useful in identifying patients who are most appropriate for chemotherapy alone.

Central nervous system involvement in T-cell lymphoma: A single center experience.

Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

de Quervain's thyroiditis: A review of experience with surgery.

BACKGROUND: de Quervain's thyroiditis is an inflammatory condition of the thyroid mostly treated medically, rarely requiring surgical treatment. We intend to review the surgical experience with de Quervain's thyroiditis at a tertiary cancer center over a period of 22years. METHODS: A retrospective review of medical records from 1992 to 2014 at a tertiary cancer center was performed and all patients with a histopathological diagnosis of de Quervain's thyroiditis were included. RESULTS: Ten patients with a histopathological diagnosis of de Quervain's thyroiditis were included in the study. One patient in the study presented with dysphagia due to the goiter. The remaining patients presented with thyroid nodules. None presented with typical symptoms of the disease. Seven of the ten patients that had been evaluated for a goiter at an outside facility underwent fine needle aspiration cytology. Of the seven patients, one patient was suspected to have medullary carcinoma of the thyroid, two had follicular neoplasia, and the others had indeterminate nodules. Eight of the ten patients underwent surgery for suspected malignancy, with eight receiving a total thyroidectomy and two patients getting a thyroid lobectomy with isthmusectomy. Two patients had an abnormally hard gland to palpate during surgery with the others not having any suspicious findings. Seven of the ten of the patients had lymph node sampling from level 6 and all were benign on final pathology. The mean duration of post-operative follow-up was 15months. There was no morbidity associated with surgery in any of these patients with eight of the ten patients requiring thyroid hormone replacement. None of the patients needed further neck surgery for thyroid disease. CONCLUSION: de Quervain's thyroiditis is an inflammatory condition of the thyroid that is rarely treated surgically. However when presentation is atypical and the FNAC is inconclusive or is suspicious for a malignancy, patients receive surgery putting them at a risk for morbidity. Good clinical assessment with combined use of ultrasound with FNAC especially read by an experienced cytopathologist has the potential to reduce unnecessary operative intervention.

Very low utility of surveillance imaging in early-stage classic Hodgkin lymphoma treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy.

BACKGROUND: This study evaluated the need for surveillance imaging in early-stage classic Hodgkin lymphoma (cHL) after planned combined-modality therapy (CMT). METHODS: Primary early-stage cHL patients who underwent CMT were included. Positron emission tomography (PET)/computed tomography (CT), CT, or both were performed at the initial staging, during or after chemotherapy, and for at least 2 years during follow-up. Imaging studies and medical records were reviewed to determine if and when relapse had occurred. Radiation doses and costs were also calculated from follow-up imaging. RESULTS: The study included 78 patients with a median follow-up of 46 months; 85% of the patients had stage II disease (32% with bulky disease). Four of 77 interim PET scans were positive; none of these patients relapsed during follow-up, which ranged from 24 to 80 months. After a total of 466 follow-up imaging studies (91% with CT and 9% with PET/CT), no cHL relapse was detected. Eleven abnormal findings were noted on surveillance imaging: 9 were false-positives, and 2 were second primary malignancies. The average cumulative dose per patient from follow-up imaging was 107 mSv, which translated into an estimated lifetime excess cancer risk of 0.5%; the estimated total costs were $296,817 according to Medicare reimbursements. CONCLUSIONS: Surveillance imaging with either CT or PET/CT can be omitted safely for early-stage cHL treated with a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine and radiation therapy because the risk of relapse is extremely low. This observation also applies to patients with bulky disease. The elimination of surveillance imaging will also reduce healthcare expenses and cumulative radiation doses in these predominantly young patients.

Cost-effectiveness analysis of papillary thyroid cancer surveillance.

BACKGROUND: The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories. METHODS: Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services. RESULTS: The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively. CONCLUSIONS: The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured.

Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era.

Therapeutic options for limited-stage diffuse large B cell lymphoma (DLBCL) include short- or full-course R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) ± radiotherapy. The optimal treatment remains unclear. The prognostic value of cell-of-origin (COO) in early stage DLBCL is unknown. Patients with limited-stage DLBCL (stage I or stage II, non-bulky) treated with R-CHOP ± involved field radiotherapy (IFRT) from 1999 to 2012 were included. COO by the Hans algorithm was analysed in a subset of patients. Of 261 patients, 30% were stage I (N = 82), 37% stage IE (N = 96), <1% stage IXEE (N = 1), 18% stage II (N = 46) and 14% stage IIE (N = 37). The stage-modified International Prognostic Index stratified patients into prognostically relevant groups. There was no significant difference in progression-free survival (PFS) or overall survival (OS) for patients in the germinal centre B-cell-like (GCB; n = 65) and non-GCB cohorts (n = 22). Seventeen patients received R-CHOP × 3-4 cycles (Arm A), 147 received R-CHOP × 3-4 cycles + IFRT (Arm B), 48 received R-CHOP × 6 cycles (Arm C), and 50 received R-CHOP × 6 cycles + IFRT (Arm D). The outcomes were excellent, with 5-year PFS of 82% and 5-year OS of 93%, and were similar across the 4 treatment groups. In the rituximab era, outcomes for limited-stage DLBCL, regardless of treatment approach, were excellent. Baseline COO was not a significant prognostic factor in patients treated with short-course R-CHOP + IFRT.

Prognostic Value of FDG PET/CT before Allogeneic and Autologous Stem Cell Transplantation for Aggressive Lymphoma.

PURPOSE: To determine the prognostic value of performing fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) before allogeneic and autologous stem cell transplantation (SCT) in patients with aggressive lymphoma. MATERIALS AND METHODS: A HIPAA-compliant retrospective review was performed under institutional review board waiver. Patients with aggressive lymphoma underwent allogeneic or autologous SCT between January 2005 and December 2010. FDG PET/CT was performed within the 3 months prior to transplantation. PET/CT images were evaluated for lesions with FDG avidity greater than that of the background liver. The relationship between pretransplantation PET and progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) was assessed with Kaplan-Meier curves and a corresponding log-rank test for categorical variables and Cox regression for continuous variables. RESULTS: A total of 175 patients were identified, of whom 73 underwent FDG PET/CT before allogeneic SCT and 102 underwent FDG PET/CT before autologous SCT. Before allogeneic SCT, 23 of 73 patients (32%) had FDG-avid lesions, and before autologous SCT, 11 of 102 patients (11%) had FDG-avid lesions. For allogeneic SCT, the 2-year PFS estimate was 68% (95% confidence interval [CI]: 56%, 82%) in patients without FDG-avid lesions, but only 35% (95% CI: 20%, 61%) for patients with FDG-avid lesions (P = .014). For autologous SCT, the 2-year PFS was 72% (95% CI: 64%, 82%) in patients without FDG-avid lesions, but only 18% (95% CI: 5%, 64%) for patients with FDG-avid lesions (P < .0001). Similar differences were seen in OS and DSS. The risk for posttransplantation recurrence correlated with higher lesional maximum standardized uptake values: for PFS, P < .0001 to P = .01; for DSS, P < .0001 to P = .002; and for OS, P < .0001 to P = .015. CONCLUSION: Performing FDG PET/CT before SCT in patients with aggressive lymphoma has prognostic value. For patients with aggressive lymphomas, the presence of FDG-avid lesions at PET/CT performed before allogeneic and autologous SCT indicates a lower likelihood of SCT success.

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

PURPOSE: We investigated reflectance confocal microscopy (RCM) as a possible noninvasive approach for the diagnosis of cancer and real-time assessment of surgical margins. EXPERIMENTAL DESIGN: In a phase I study on 20 patients, we established the RCM imaging morphologic features that distinguish oral squamous cell carcinoma (OSCC) from normal tissue with a newly developed intraoral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology. Five RCM videos from the tumor and five from normal surrounding mucosa were collected on each patient, followed by a 3-mm punch biopsy of the imaged area. An experienced RCM reader, who was blinded to biopsy location and histologic diagnosis, examined the videos from both regions and classified each as "tumor" or "not tumor" based on RCM features established in phase I. Hematoxylin and eosin slides from the biopsies were read by a pathologist who was blinded to RCM results. Using histology as the gold standard, we calculated the sensitivity and specificity of RCM. RESULTS: We report a high agreement between the blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. CONCLUSIONS: RCM imaging is a promising technology for noninvasive in vivo diagnosis of OSCC and for real-time intraoperative evaluation of mucosal surgical margins. Its inherent constraint, however, stems from the diminished capability to evaluate structures located at more substantial depths within the tissue.

One committee to review it all: A single, multi-disciplinary COVID-19 research committee.

On 1/20/2020 when the first case of a novel coronavirus (COVID-19) was confirmed in Washington state, its major impact was unknown. Memorial Sloan Kettering Cancer Center's (MSK) Hospital Incident Command System (HICS) was activated on 2/5, with our first COVID-19 case identified in early March. By 3/17, our Protocol Activation and Human Research Protection Program was fully remote and on 3/23, MSK leadership requested the creation of the COVID-19 Research Committee. Given the race to identify safe and effective treatments for COVID-19, modifications to workflows and review processes were needed. The goal was to provide quick access to COVID-19 treatments to our patients by creating a COVID-19 Committee as a "one-stop" committee, providing comprehensive review of clinical research related to COVID-19 including scientific review mandated by the Cancer Center Support Grant (CCSG) guidelines, prior to IRB review and protocol activation. Protocols that were reviewed by the COVID-19 Committee opened to accrual in an unprecedented 44 days from submission to the committee to open to accrual. Patients were accrued on most of the therapeutic protocols within 1 day of opening. These statistics have prompted our institution to explore how more protocols can benefit from this "one-stop" committee structure.