Years Of Initial Therapy Research Articles

Abstract 2922: Sensory innervation as a novel driver of ovarian cancer progression

Abstract One of the main challenges currently faced in ovarian cancer treatment is that the primary platinum/taxane therapy used to treat patients does not meaningfully extend survival. The overall survival for ovarian cancer patients with advanced disease is less than 30% with most patients recurring within 5 years of initial therapy. Once resistant disease develops there are few second line therapy options, which inevitably leads to disease progression. Thus, there is a critical need to identify new therapies that can overcome ovarian cancer chemoresistance and produce meaningful increases in patient survival. In recent years, new efforts have focused on targeting the tumor microenvironment (TME), the complex mixture of non-cancer cells that surround and support the cancer cells within the tumor. Different strategies have evolved to target the TME, such as immune checkpoint inhibitors or angiogenesis inhibitors. However, these TME targeting therapies have limited effect when used to treat ovarian cancer patients. Most ovarian tumors have a microenvironment that is highly immunosuppressive and do not respond or are resistant to angiogenesis inhibitors. Thus, new TME targeting therapies must be developed that can induce a therapeutic effect in ovarian tumors and can be used to treat most ovarian cancer patients. A novel TME component ripe for therapeutic targeting are the nerve fibers that infiltrate tumors in a process termed tumor innervation. Recent studies in several cancers have shown that tumor innervation can promote tumor growth/metastasis. However, in ovarian cancer the role of innervation in promoting cancer progression remains undefined. Here we show that Transient Receptor Potential cation channel subfamily V member 1 (TRPV1)+ sensory innervation plays a significant role in driving ovarian cancer growth and metastasis. Analysis of patient samples shows that sensory nerve fiber innervation is much higher in ovarian tumors vs benign reproductive tissue. In addition, ablation of TRPV1 sensory nerve fibers in vivo causes reduced tumor burden and prolongs survival in a syngeneic mouse model of ovarian cancer metastasis. Taken together, our results establish TRPV1+ sensory innervation as a novel driver of ovarian cancer growth/metastasis and a potential therapeutic target for ovarian cancer treatment. Citation Format: Matthew Knarr, Katherine Cummins, Dusan Racordon, Hunter Reavis, Timothy Lippert, Ryan Hausler, Priyanka Rawat, Suyeon Ryu, Jamie Moon, Dave Hoon, Roger Greenberg, Paola Vermeer, Ronny Drapkin. Sensory innervation as a novel driver of ovarian cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2922.

Patterns of Care and Outcomes for Non-Metastatic Prostate Cancer in the United States: Results of the CancerMPact® Survey 2018.

PurposeWe describe patterns of care and treatment outcomes for non-metastatic PCa (nmPCA), either hormone-sensitive or castration-resistant, in the United States of America (USA) in 2018.MethodsA survey (CancerMPact®) recruited physicians nationwide to answer an online questionnaire about how they treated patients with nmPCA. Questions covered aspects of treatment at all disease stages. Board-certified urologists and oncologists with at least five years of clinical practice and who treated at least 30 PCa patients monthly were included.ResultsThe survey included responses from ninety-four physicians with an average of 17.5 years of clinical practice, who had treated a combined average of 4415 patients with nmPCA per month in 2018. Approximately 40% of patients in stage I were managed with either active surveillance or observation/no therapy, decreasing to 20%, 8% and 6% in stages II, III and IV(M0), respectively. Intensity-modulated radiotherapy was favored over other radiotherapy modalities, with rates of use ranging between 60% and 69% depending on disease stage. Leuprolide as monotherapy or in combination with enzalutamide, abiraterone or bicalutamide were the most common systemic treatment options for non-metastatic hormone-sensitive PCa (nmHSPC) patients with the first or second recurrence. Only 16.5% of non-metastatic castration-resistant PCa (nmCRPC) patients did not relapse within five years of initial therapy for nmCRPC.ConclusionWhile PCa treatment recommendations are rapidly changing due to advances in treatment, we observed great concordance between their most current versions and real-world data treatment patterns reported by US physicians.

Cost-effectiveness analysis of allogeneic versus autologous stem cell transplant versus chemo-immunotherapy for early relapse of follicular lymphoma within 2 years of initial therapy.

This study compared the quality-adjusted effectiveness and costs of three treatment options for transplant-eligible patients with early progression (POD24) of follicular lymphoma. A Markov decision-analytic model using a 20-year time horizon was used to compare allogeneic stem cell transplant (alloSCT), autologous stem cell transplant (ASCT), and chemo-immunotherapy (O-CHOP). For second relapse/refractory disease, novel therapy use was modeled, including lenalidomide and rituximab/obinutuzumab, and PI3K inhibitors (PI3Ki). Costs were considered from a Canadian public health payer's perspective. Probabilistic analyses (10,000 simulations) demonstrated that at a willingness-to-pay threshold of $50,000, ASCT was most cost effective 60% of the time. ASCT resulted in more life years (10.2 vs. alloSCT 9.9 vs. O-CHOP 10.0) and quality-adjusted life years (7.5 vs. alloSCT 6.6 vs. O-CHOP 7.4), with the lowest direct costs ($190,128 CAD). In sensitivity analyses, the model was robust to key variables, including differing probabilities of progression, non-relapse mortality, graft-versus-host-disease (GVHD), costs of treating GVHD, costs of PI3Ki, and probability of secondary malignancy from ASCT. However, if patients were older than 65 years or their life expectancy was less than 10 years, chemo-immunotherapy was the preferred strategy. When considering cost, effectiveness, and toxicities, the preferred treatment strategy for most patients with POD24 follicular lymphoma is ASCT.

PCN345 PATTERNS OF CARE AND OUTCOMES FOR NON-METASTATIC PROSTATE CANCER IN THE UNITED STATES: RESULTS OF THE CANCERMPACT® SURVEY 2018

To describe patterns of care and treatment outcomes for non-metastatic PCa, either sensitive or resistant to castration, in the United States of America in 2018. This survey (CancerMPactÒ) recruited nationwide physicians to answer an online questionnaire about how they treated their patients with non-metastatic PCa. Questions were detailed to cover aspects of the treatment for all stages of the disease. Only board-certified urologists and oncologists with at least five years of clinical practice, and who treated at least 30 PCa patients monthly were included in the study. The survey comprises responses from ninety-four physicians with an average of 17.5 years of clinical practice, who collectively had treated an average of 4,415 patients with non-metastatic PCa per month in 2018. Around 40% of the patients in stage I were managed with either active surveillance or observation/ no therapy, with that rate dropping to roughly 20%, 8% and 6% in stages II, III and IV(M0), respectively. Intensity modulated radiotherapy was largely favored over other radiotherapy modalities, with rates of used ranging from 60% to 69% depending on disease stage. Abirateron and Enzalutamide combined with Leuprolide were the most common systemic treatment options for non-metastatic hormone-sensitive PCa (nmHSPC) patients with a second recurrence; they also rated among the four top regimens among nmHSPC patients with a first recurrence for all stage subgroups. Over 60% of non-metastatic castration-resistant PCa (nmCRPC) patients received a second-generation hormone as initial therapy. Only 16.5% of nmCRPC patients did not relapse within five years of initial therapy for nmCRPC. Despite a fast pace progress of PCa treatment recommendations, we observed great concordance between their most current versions and real-world data treatment patterns reported by US physicians.

RARE-06. A CASE OF RECURRENT SUPRATENTORIAL EXTRAVENTRICULAR ANAPLASTIC EPENDYMOMA IN ADULT

Abstract Supratentorial extraventricular anaplastic ependymoma (SEAE) in adults is a relatively rare intracranial tumor. Because of very low prevalence, SEAE has been reported only a few cases. According to a recent study, SEAE is associated with a poor prognosis and there is no definite consensus of optimal treatment. We report a case of an adult SEAE patient who had no recurrence until seven years after gross total resection(GTR) followed by conventional radiotherapy. A 42- year- old male had a persistent mild headache, left facial palsy, and dysarthria. Preoperative neuroimaging revealed an anaplastic astrocytoma or supratentorial ependymoma in the right frontal lobe. A GTR was performed, followed by adjuvant radiotherapy. Histologic and immunohistochemical results revealed anaplastic ependymoma, After seven years of initial therapy, a regular follow-up MRI showed a 3-cm –sized partially cystic mass in the same area as the initial tumor. The patient underwent a craniotomy, and a GTR was performed. Histopathologic examination revealed recurrence of the SEAE. External radiotherapy was performed. The patient has been stable without any disease progression or complications for 12 months since the surgery for recurrent SEAE

Early progression of disease as a predictor of survival in chronic lymphocytic leukemia.

Chemoimmunotherapy for chronic lymphocytic leukemia (CLL) promotes clonal evolution of aggressive clones, which in some patients may lead to early progression of disease (POD). We studied the prognostic value of early POD in a cohort of patients with CLL enrolled between 2010 and 2014 in the Connect CLL Registry. Overall, 829 eligible patients receiving first-line therapy were categorized into 3 groups: early POD (progression <2 years after treatment initiation), late POD (progression ≥2 years after treatment initiation), and no POD as of 1 May 2017. Baseline demographics, treatment characteristics, and overall survival (OS) were analyzed. Logistic regression models identified independent predictors of early POD; Cox regression models were used to evaluate the risk of early POD. With a median follow-up of 48.8 months, 209 (25.2%), 162 (19.5%), and 458 (55.3%) patients had early, late, and no POD, respectively. Patients with early POD were older and had inferior response to similar first-line treatment regimens vs late and no POD groups (overall response rate: 53% vs 80% vs 84%). Patients with early POD were more likely to have unfavorable-risk cytogenetics (del[11q]/del[17p]) than patients with no POD (34% vs 20%; P = .04). Early POD was associated with an inferior OS across all patients (hazard ratio, 3.6; 95% confidence interval, 2.6-5.1; P < .01) and in patients treated with fludarabine, cyclophosphamide plus rituximab, and bendamustine plus rituximab (P < .05). Early POD within 2 years of first-line therapy is a robust clinical prognostic factor for inferior OS in patients with CLL. The Connect CLL Registry was registered at www.clinicaltrials.gov as #NCT01081015.

Primary refractory Hodgkin lymphoma: Limited options and poor survival—but not always

Primary refractory Hodgkin lymphoma: Limited options and poor survival—but not always

Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study

There is accumulating evidence that long-term disability and disease progression in multiple sclerosis (MS) are due to prolonged sodium channel opening along demyelinated axons. Despite good evidence in animal models of MS that partial voltage-gated sodium channel (VGSC) blockade reduces disease progression, little is known about its effects in patients, despite widespread use of such agents in the symptomatic management of MS. To determine if long-term exposure to the VGSC-blocking drug carbamazepine (CBZ) alters disease progression in MS. Using a retrospective chart review of patients diagnosed with MS, we compared progression of disability between patients exposed the VGSC blocker CBZ with those who were not exposed to the drug. Both whole-group and matched case-control analyses were performed after correcting for the influence of age, gender, MS subtype, expanded disability status score at diagnosis, use of disease-modifying therapy, and year of initial therapy. The multiple sclerosis severity scale (MSSS) was used as a measure of disease severity. The primary outcome measure was MSSS score difference between groups. Four hundred patients were included; 51 received CBZ symptomatic therapy (average duration of therapy 27 months). There was no significant difference in mean MSSS between the two groups in either the whole group comparison (p = 0.63) or the matched analysis (p = 0.12). Despite preclinical evidence suggesting a neuroprotective role of VGSC blockers in animal models of MS, this retrospective study suggests that long-term exposure to the VGSC-blocking drug CBZ fails to alter long-term disability and disease progression in MS patients.

Management of Low-Grade Gliomas in Childhood

Management of Low-Grade Gliomas in Childhood

Outcomes of Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Patients (pts) After Surviving 5 Years of Initial Therapy with Interferon Alpha (IFN), Imatinib (IMA) or Allogeneic Stem Cell Transplantation (ASCT)

Abstract 2001▪▪This icon denotes a clinically relevant abstract Introduction:IFN and ASCT were the most commonly used treatment modalities for CML before 2001. The introduction of IMA as the preferred treatment for CML changed the treatment paradigms for this disease. CML pts are now expected to live longer and responses are prolonged in most cases. However, long-term outcomes including late relapses, durability of response, side effects, and late development of new medical conditions are largely unknown. Methods:We performed a chart review of pts with CML in CP treated at our institution who have survived at least 5 yrs of their initial IFN or IMA therapy, or 5 yrs after ASCT, to analyze their long-term outcome, risk of late relapse, and emergence of late side effects or new medical health problems. Results:469 pts with CML CP treated at our institution between 1981 and 2006 survived at least 5 yrs on their initial CML treatment. One hundred twenty five pts are described in this analysis: 25 pts in the IFN group, 50 pts in the IMA group (400 mg/d), and 50 pts in the ASCT group. Pts received their initial treatment a median of 1 month (range, 0.3 to 11), 1 month (range, 0 to 7), and 13 months (range, 1 to 126) from diagnosis, respectively. Median time on initial therapy for the IFN and IMA groups was 6.4 yrs (range, 5–8.5) and 10.8 yrs (range, 5.1–11.5). Characteristics of the pts at time of diagnosis were as follows: hypertension (HTN) was present in 12%, 30% and 2% of the IFN, IMA, and ASCT pts, respectively; cardiac disease in 12%, 8% and 2%, respectively; thyroid disease (Thy) in 8%, 8% and 2%, respectively. Median number of medications (MEDS) per patient at baseline was 1 (range, 0–5), 1 (range, 0–13) and 0 (range, 0–4), respectively. Complete cytogenetic response (CCyR) was obtained in 76% (n=19), 96% (n=48) and 100% (n=50) of the pts, respectively. Time to best CyR was 17.1 months (mos) (range, 6–59.1), 7.2 mos (range, 2.4–64.2) in the IFN and IMA groups, respectively. Loss of cytogenetic response after 5 years occurred in 91% (n=21, 2 pts had no initial response, 2 pts remained in CCyR), 10% (n=5) and 6% (n=3), respectively. Twenty pts (80%) on the IFN cohort were switched to IMA at a median of 7.4 yrs (range, 5.3–13.3) after diagnosis (19 occurring between yrs 2000 and 2001). Of these 20 pts 75% (n=15) achieved MMR or better after a median of 4 yrs (range, 0.6–10.2) on IMA. New medical problems that developed at the 5 year mark were a follows: Thyroid problems in 8%, 0% and 10%, respectively, HTN in 0%, 2% and 14%, respectively; cardiac in 0%, 4% and 0%, respectively; and other in 44%, 22%and 58%, respectively. Median MEDS per patient at the 5 year mark was 2 (range, 0–7), 4 (range, 1–12) and 2 (range, 0–15), respectively. New medical problems that developed by last follow up were a follows: Thyroid problems in 4%, 6% and 0%, respectively; HTN in 4%, 18% and 10%, respectively, cardiac in 8%, 4% and 4%, respectively; osteoporosis in 0%, 0% and 6%, respectively, and other in 44%, 32% and 26%, respectively. Median Meds per patient at last follow up was 4 (range, 0–19), 6 (range, 1–16) and 2 (range, 0–25), respectively. Secondary malignancies occurred in 8%, 10% and 12% of patients, respectively. Pts continued to be on initial treatment in 16% (n=4), 94% (n=47) and 94% (n=47), respectively. At date of last follow up, late relapses (beyond 5 yrs of initial therapy) occurred in 72% (n=18), 8% (n=4) and 2% (n=1), respectively. At median follow up of 18, 11, and 14 yrs respectively, 76% (n=19), 92% (n=46) and 92% (n=46) are alive, 64% (n=16), 86% (n=43) and 90% (n=45) in CCyR. Conclusion:CP CML pts treated with IMA or SCT and surviving 5 yrs beyond initial treatment have low incidence of late relapses. New medical problems including heart disease and secondary malignancies may occur in some pts, but most pts are still alive. Pts with CML require prolonged medical care even in the setting of lasting remissions. Disclosures:Jabbour:BMS: Honoraria; Pfizer: Honoraria, Research Funding; novartis: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding.

Nonmelanoma Skin Cancer

Nonmelanoma Skin Cancer

Balancing Fertility and Oncologic Outcomes: Can We Have Our Cake and Eat It Too?

During the last decade, gynecologic oncologists and pathologists have begun to reconsider which clinical and pathologic factors effect outcomes in patients with borderline tumors of the ovary. These tumors of low malignant potential lack the deep stromal invasion ([ 5m m or [10 mm 2 ) of their invasive carcinoma counterparts. And unlike epithelial carcinomas, which have six different subtypes (serous, endometrioid, mucinous, clear cell, transitional, and undifferentiated), borderline tumors of the ovary are almost exclusively either serous or mucinous. Serous borderline tumors tend to be smaller than their mucinous counterparts and rarely have areas of invasive carcinoma in the same specimen. Furthermore, they seldom recur once removed; however, when they do, they typically return as recurrent borderline histology and rarely undergo malignant transformation into low-grade serous carcinoma. It is exceedingly rare for a serous borderline tumor to recur as a high-grade carcinoma. Mucinous borderline tumors, on the other hand, seem to be a step along the continuum from normal to invasive mucinous carcinoma. Pathologic specimens may have areas of normal ovary, benign mucinous cystadenoma, borderline tumor, and high-grade invasive mucinous carcinoma side by side with one another. Because these neoplasms often can be [10 cm in size at surgical resection, making frozen section exclusion of invasive carcinoma difficult, most gynecologic oncologists perform a modified staging procedure, which includes appendectomy for all mucinous neoplasms (benign or borderline) in the event that final pathology returns an invasive carcinoma. In this month’s issue of Annals of Surgical Oncology, Koskas and colleagues 1 report their single institution experience with mucinous borderline tumors of the ovary. This study reviewed a large cohort of 97 patients seen during a 7-year period from 1997‐2004. The authors found that 9% of patients recurred as invasive carcinoma within 5 years of initial therapy. At 10 years follow-up, that number had increased to 13%. This important finding of malignant transformation is significantly higher than what has been reported in the literature to date. Many of these patients had undergone only an ovarian cystectomy in an effort to preserve fertility. The authors challenge the traditional philosophy that borderline tumors of the ovary are relatively benign and that even when they do recur they tend to be indolent with minimal effect on mortality. In addition, they suggest that cystectomy is likely insufficient treatment of borderline tumors and recommend at least complete oophorectomy. Although retrospective in nature, this study has many strengths. Most importantly, all pathologic specimens were reviewed at their institution. Because 80% of mucinous tumors of the ovary are extraovarian in origin, it is imperative that these specimens are centrally

Abstract 4213: Lentiviral shRNA screen testing a gene signature of breast cancer stem cells using high throughput mammosphere assays

Abstract One in 8 women in the US suffer from breast cancer and current treatments have reduced the rate of cancer dependent deaths, the major problem facing this field is the high likelihood of relapse within 5-10 years of initial therapy. Relapse might be caused by the presence of cancer stem cells in the tumor which are not inhibited by traditional therapies and thus may require therapies that target this subpopulation of cells. We have recently published a gene signature which is derived from an overlap between CD44+/CD24-/low vs. all other cell subpopulations, and cancer-derived Mammosphere (MS) vs. bulk tumor which we reasoned will best represent the tumor-initiating or “cancer stem cells. We found that 477 genes were differentially expressed in the combination group of which 185 of these were highly expressed in CD44+/CD24-/low cells and in MS, a highly significant overlap (p&amp;lt;1.0E-9, one-sided Fisher's exact). The rest of the 292 genes demonstrated a reduction in expression in the CD44+/CD24-/low cells and cancer-derived MS vs. all other cells and bulk tumors, respectively (p&amp;lt;5.0E-5, one-sided Fisher's exact). We then proceed to test our gene signature by screening this entire list of genes for its role in MS. We created a library comprises 14 plates containing approximately 1193unique shRNA constructs, with 3-4 shRNA constructs per gene, thereby targeting 493 unique genes. The library is designed and constructed on a “one gene, one well” structure, such that each sequence validated lentiviral shRNA construct targeting an individual gene is located in a unique well of a 96-well plate. Using SUM159 cells that were transduced with individual lentiviruses representing our previously identified genes (efficiency ∼80%), along with a positive control lentivirus targeting Bmi1, a polycomb group gene known to be required for self-renewal of many stem/progenitor cell types, a non-specific negative control lentivirus targeting firefly luciferase, as well as untreated cells. In each of the transduced population cells will be plated in a 96 well dish at a density of 2,000 cells/well in serum-free medium supplemented with B27 nutrients, bFGF, EGF. MSs were allowed to form for 4 days, and then counted using Gelcount (Oxford Optornix). The MSs were trypsinized and replated in the same plate to form secondary mammospheres and primary and secondary mammosphere formation efficiency was calculated. The primary &amp; secondary MSFE was determined for all the shRNAs and we identified 151 shRNAs while the secondary MS formation identified 63 shRNA's of which 13 shRNAs were common that demonstrated significant change (p&amp;lt;0.05) in MS formation with respect to control. This gives us a set of targets that need to be validated by testing them in another cell line, which in turn will provide pharmaceutical targets to eliminate cancer stem cells. Top 5 targets will be tested in tumor xenografts to test clinical relevance of these therapies. 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 4213.

Long-Term Outcome of Autologous Stem Cell Transplantation (ASCT) for Hodgkin Lymphoma (HL) in the ABVD Therapeutic Era.

ASCT is the standard therapy for relapsed HL. However, the majority of published studies suggesting benefit of ASCT for relapsed HL include relatively young patients (pts) with favorable prognostic features, and have relatively short follow-up. Moreover, very little data exists on the outcome of pts who experience progression of HL after ASCT. To determine the long-term outcome of ASCT in the modern, “ABVD-era”, and the impact of allogeneic transplantation in pts who fail ASCT, we reviewed all pts with HL who were treated with ASCT between 1990 and 2005 at the University of Rochester. 117 pts (44% female; 89% Caucasian) with documented HL were treated with ASCT for relapsed or refractory HL. At ASCT, median age was 34 years (range 19–66). 75% of these pts were treated initially with ABVD or MOPP-ABVD hybrid therapy. Histology was: NS (n=82), mixed cellularity (n=20), LP (n=6), LD (n=3), and classical NOS (n=6). 32% of pts had relapsed within 1 year of initial therapy, and 25% were refractory to therapy prior to ASCT. Conditioning regimens at ASCT were BEAC (n=80); BEAM (n=28); CBV (n=1); Cy/TBI (n=8). 49% of pts received XRT following ASCT. Median follow-up of entire cohort exceeded 5 years. At 5 years, overall survival (OS) for entire population was 50%, and event-free survival (EFS) was 38%. As expected, pts older than 45 yrs of age (n=21, p=0.06) and pts who relapsed within 1 year of initial therapy (p=0.0004) had an inferior OS after ASCT. In total, 49 pts have died; of these, 30 pts died of HL. 19 deaths occurred in remission: 9 were conditioning-related within the first 100 days of ASCT; 3 were from secondary malignancies (2 AML, 1 NHL), 1 from colitis, 1 from pulmonary fibrosis, and 5 with unknown cause. 9 of the deaths occurred more than 5 yrs after ASCT. 54 pts had progression of HL post ASCT; median survival for this group was 2.1 years after ASCT. 14 of these pts (26% of pts who failed ASCT) underwent allogeneic transplantation. 8 of these patients have died: 5 from progression of HL, 2 from pulmonary toxicity, and 1 from GVHD. Of the 5 remaining pts, 1 has progression of HL after allogeneic transplantation, and 3 have chronic GVHD. We conclude that ASCT remains a curative option for patients relapsing after ABVD, as there is a clear plateau on the relapse free survival curve after 5 years. Primary refractory disease and older age at ASCT dramatically affects outcome. In this modern era, deaths in remission after ASCT remain a significant problem due to both short-term and long-term toxicities of therapy. The risk of progression of HL persists until 5 years after ASCT, emphasizing the importance of prolonged follow-up. Although some pts who progress with HL after ASCT may live for years with a seemingly indolent form of HL, there is no plateau on the survival curve, and the majority of pts who progress after ASCT are not alive 2 years post ASCT. Allogeneic transplantation has not yet had a significant impact on OS for this group of pts. Novel approaches are clearly needed for the majority of pts who progress after ASCT, particularly older patients at ASCT and patients with primary induction failure.

USE OF SECOND TREATMENT FOLLOWING DEFINITIVE LOCAL THERAPY FOR PROSTATE CANCER: DATA FROM THE caPSURE DATABASE

Purpose We compare secondary cancer treatment use in patients who underwent definitive local treatment for prostate cancer. Materials and Methods The rate of second cancer treatment was determined in patients who underwent radical prostatectomy (1,254), radiotherapy (499) or cryosurgery (141) using data from the CaPSURE database, a longitudinal disease registry of patients with prostate cancer. Second treatments started within 3 months after initial treatment were defined as adjuvant and those started more than 3 months were defined as nonadjuvant. Using a parametric regression model of survival analysis, second treatment rates were adjusted for differences in clinical and demographic characteristics, and duration of followup among groups. Results Of the patients 4% received a second adjuvant treatment and 17% received a second nonadjuvant treatment within 3 years of initial therapy. Adjusted rates of nonadjuvant second treatment were lowest after radical prostatectomy, and 34 and 88% higher after radiation and cryosurgery, respectively (p = 0.01). This finding was most evident in patients with pretreatment prostate specific antigen 10.0 ng./ml. or less, clinical stage T2N0M0 disease, or Gleason score 6 or less on diagnostic biopsy, and in those classified as low risk for recurrence based on a combination of these parameters (p = 0.004). Conclusions Approximately 1 in 5 patients receive second cancer treatment within a mean of 3 years following initial local treatment for prostate cancer. Our data suggest that the likelihood of receiving second treatment was lowest in patients initially treated with radical prostatectomy.

Early Myeloablative Therapy for Multiple Myeloma

The value of early myeloablative therapy supported by autologous bone marrow or blood progenitor cells was assessed in 72 patients with multiple myeloma who were treated within 1 year of initial therapy. Forty-five patients were consolidated during remission, and 27 patients were treated for primary refractory disease. Outcomes were compared with those of similar patients who did not receive intensive treatment primarily for socioeconomic reasons. Among patients who had responded previously, myeloablative therapy increased the rate of complete remission from 5% to 45% (P < .01) but did not prolong progression-free intervals or survival times. The same treatment controlled the myeloma in 70% of patients with primary resistant disease and prolonged the median survival from 37 to 83 months (P = .03). Intensive treatment for primary resistant myeloma administered later in the disease course resulted in significantly lower response rates and shorter progression-free intervals. Current myeloablative regimens supported by autologous stem cells appeared useful primarily in patients with primary resistant disease during the first year of therapy.

Squamous cell carcinoma of the oral cavity. A review of 176 cases with application of malignancy grading and DNA measurements

This retrospective study comprised 176 patients with squamous cell carcinoma of the oral cavity treated at The Linköping University Hospital over a 19-year period. Clinical parameters, microscopic malignancy grading (according to Jakobsson et al. and Glanz and Eichhorn), DNA cytofluorometry, analysis of therapeutic modalities and statistics regarding survival and prognosis are reported. The mean age was 70 years with a male: female ratio of 1.3:1 One hundred and four patients had T1 or T2 tumours and 109 an N0 neck. Cervical lymph node metastases were more frequent in patients with larger tumours (T3 + T4) than in those with smaller (T1 + T2) (P less than 0.01), in tumours with a high malignancy grading compared to those with a low (P less than 0.05) and in DNA non-diploid tumours compared to diploid ones (P less than 0.001). The aneuploid tumours responded better to preoperative radiotherapy than did diploid (P less than 0.01) or polyploid (P less than 0.05) tumours. Eighty-nine per cent of the recurrences occurred within 1 year of initial therapy. Secondary treatment was successful in 15 of 37 (41%) patients in whom the tumour recurred either at the primary site or in regional lymph nodes, but only in 1 of 8 (12%) with recurrences in both locations. Surgery alone or combined with radiotherapy resulted in equivalent survival rates for tumours in stages I and II. In advanced stages combined radiotherapy and surgery gave better survival figures than either modality alone (P less than 0.01; Kaplan-Meier). The presence of lymph node metastases (P less than 0.001), tumour size (P less than 0.01) and tumour ploidy (P less than 0.005) were the only clinical and histological parameters that significantly influenced survival (Cox regression analysis). Twenty-four patients developed a secondary primary malignancy; 21 of these were located in the aerodigestive tract.

Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin

The clinical and pathologic features of 22 examples of pure ductal squamous cell carcinoma (SqCC) of the breast are reported. All patients were women with a mean age of 53 years. Only two of the 19 women with axillary dissection had metastases, but one woman had a positive supraclavicular lymph node in the presence of negative axillary nodes. All metastases were squamous carcinoma. All patients were eligible for a minimum of 5 years' follow-up; the cumulative 5-year disease-specific survival rate was 63%. Eight women developed metastases and one also developed local recurrence, all within 2 years, and all eight died from tumor within 4 years of initial therapy (mean, 2 years). Prophylactic postoperative radiation therapy and radiation for lymph node metastases at initial surgery did not prolong survival as four of the five recipients died from tumor. Although there were no statistically significant gross or histologic differences between recurrent and nonrecurrent neoplasms, larger neoplasms tended to metastasize. Immunohistochemical study for S-100 protein identified an immunoreactive cell component in five of seven neoplasms tested. This and light microscopic findings suggest myoepithelial proliferation, differentiation, or origin.

Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma

The clinical and pathologic features of 26 examples of a histopathologically distinct form of metaplastic carcinoma of the breast are reported. All neoplasms had overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix without an intervening spindle cell zone or osteoclastic giant cells. Therefore, we designate this distinctive form of metaplastic carcinoma as “matrix-producing carcinoma” (MPC). All patients were women, the average age was 58 years, and all patients were eligible for a minimun of 5 years follow-up (mean follow-up period, 8.6 years). Twenty-three patients were treated by a form of mastectomy and three were treated by local excision. The 5-year survival rate for patients following mastectomy or partial mastectomy was 70%, contrasted with 50% for patients treated by local excision. The cumulative 5-year survival rate for MPC was 68%. All of the nine lesions that recurred did so within 2.5 years of initial therapy. Eight of these patients (89%) died from tumor within 4 years of initial therapy. The ninth was alive at last contact. Radiation and chemotherapy were of limited effectiveness. Significant features of the neoplasm associated with progression were large size, diffuse cellularity of the stromal matrix, and atypical cartilaginous metaplasia. Ultrastructural examination of one case and immunohistochemical evaluation of 12 cases revealed MPC to have myoepithelial characteristics.

Prognostic significance of tumor emboli in intramammary lymphatics in patients with mammary carcinoma.

Approximately 20% of patients with invasive mammary carcinoma who do not have axillary metastases develop recurrent carcinoma within 10 years of initial therapy. There is clearly a need to identify those patients most likely to develop recurrences in this group since they may benefit from adjuvant therapy. This study was undertaken to evaluate the prognostic significance of intramammary lymphatic tumror emboli in patients with invasive breast carcinoma who did not have lymph node metastases. Twenty-three such patients treated in 1974 and 15 from 1964 were compared with matched groups of control patients who did not have lymphatic emboli. About 43% of patients with lymphatic emboli and 4% of those without emboli followed for 5 or more years in the 1964 group developed distant metastases (p less than 0.001). Local recurrences were found in only one study patient and one control in the entire series of 1964 and 1974 patients. The results suggest that among patients without axillary metastases, the finding of tumor cells in lymphatic spaces within the breast is associated with a substantial risk of distant metastases but not local recurrence.