Jeremy Sturgeon

Non-hodgkin's lymphoma of the thyroid gland: Prognostic factors and treatment outcome

Abstract Purpose: Non-Hodgkins lymphoma presenting in the thyroid gland is uncommon. A review of the Princess Margaret Hospital experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. Methods and Materials: Fifty-two patients treated at the PMH between 1978 and 1986 were identified and their records reviewed retrospectively. Staging procedures revealed 16 patients with Stage I, 28 with Stage II, and eight with Stages III or IV disease. Five patients were treated on a protocol designed for anaplastic carcinoma of thyroid and they were excluded from detailed analysis. Of 39 patients with Stages I and II disease, 18 were treated with radiotherapy alone, three chemotherapy alone, and 18 combined modality therapy. Combined modality therapy was used mainly in patients with large tumor bulk. Results: The overall 5-year actuarial survival and cause-specific survival were 56% and 64%, respectively. The overall relapse-free rate was 61% at 5 years. Among the 39 patients with Stages I and II disease, the 5-year actuarial survival, cause-specific survival, and relapse-free rate were 64%, 73%, and 66%, respectively. There were no significant differences in outcome between those treated with radiotherapy alone and those treated with combined modality therapy (cause-specific survival: p = 0.25, relapse: p = 0.06). A univariate analysis showed that the only variable to reach statistical significance was tumor bulk. Age was marginally significant while stage and histology were not statistically significant, possibly due to the fairly homogeneous distribution of patients in each of these variables. Patients with progression or relapse of lymphoma after initial treatment frequently died of disease. Isolated gastrointestinal relapses occurred in three cases, representing 27% of all relapses. Conclusion: Based on the above results, we recognize that the majority of patients with localized thyroid lymphoma require combined modality therapy and we recommend radiotherapy alone only for a small, select group of patients with Stage I disease and small tumor bulk.

Accuracy of Recorded Tumor, Node, and Metastasis Stage in a Comprehensive Cancer Center

PURPOSE The benefits of recording the tumor, node, and metastasis (TNM) stages of cancer patients are well accepted, but little is known about how accurately this is performed. An audit was performed to determine the accuracy of recorded stage and to act as a baseline before the implementation of an education program. PATIENTS AND METHODS All new patient referrals to Princess Margaret Hospital between July 1 and August 31, 1997, were reviewed. An audit panel composed of five health record technicians (HRTs) and 10 doctors was assembled. Each auditor reviewed 10% of the health record. If there was a discrepancy between the stage in the health record and the auditor stage, then the final stage was determined by the audit committee. Analysis of the agreement between the health record, the physician auditor, the HRT auditor, and the final stage was performed. RESULTS A total of 855 patients were referred with a new diagnosis of a malignancy for which there was a TNM stage system; 833 patients (97.4%) had a stage assigned. There was agreement between the health record stage and final stage in 80% (95% confidence interval [CI], 77% to 82%) of cases for clinical stage, compared with 90% (95% CI, 87% to 92%) for pathologic stage. Of the major site groups, lung was the least accurately recorded. The most common major discrepancies were due to the recording of X when a definite category could be assigned. CONCLUSION This audit demonstrates the importance of staging and provides impetus to develop staging guidelines and education programs.

Malignant teratoma of the thyroid: aggressive chemoradiation therapy is required after surgery.

Malignant teratoma of the thyroid gland is exceedingly rare in adults. Many of the cases previously reported in the medical literature have fatal outcomes because of spread of tumor refractory to treatment. We report a case of primary malignant teratoma of the thyroid in a 37-year-old woman. She was treated successfully with a combination of surgery, postoperative cis-platinum-based chemotherapy and radiation therapy to the neck, with long-term follow-up (10 years). This case and the modern experience of combined modality therapy in extragonadal germ cell tumors of the thyroid and other sites illustrate that these tumors should be managed aggressively in order to achieve best results.

Effect of filgrastim (G-CSF) during chemotherapy and abdomino-pelvic radiation therapy in patients with ovarian carcinoma

PURPOSE To evaluate the safety and effectiveness of filgrastim (granulocyte colony-stimulating factor, G-CSF) in reducing neutropenia and treatment interruptions during whole abdominal radiotherapy for ovarian cancer. METHODS AND MATERIALS Sixteen patients with ovarian cancer treated with 2 to 6 courses of cisplatin-containing chemotherapy and abdomino-pelvic radiation therapy received filgrastim for neutrophil counts <2 x 10(9)/L. Endpoints for analysis included the ability to maintain the neutrophil count in the target range, number of treatment interruptions due to neutropenia, and toxicity attributed to filgrastim. RESULTS Fourteen patients received a mean of 2.9 courses of filgrastim (each with a mean duration of 4.1 days), with no treatment interruptions due to neutropenia. The majority of neutrophil counts were maintained above the target range of 2 x 10(9)/L during treatment. Thrombocytopenia requiring treatment interruption was seen in six patients and necessitated platelet transfusions in one. Thrombocytopenia occurred at a mean abdominal radiation dose of 2207 cGy and in all but one patient was preceded by one or more episodes of neutropenia. In comparison with a control group of 31 patients treated without filgrastim there was no reduction in treatment interruptions. Four patients did not complete treatment because of persistent thrombocytopenia yet received a mean of 94% of the planned abdominal radiation dose and 69% of the planned pelvic dose. Filgrastim toxicity was limited to mild skeletal pains in six patients and a Grade 1 skin rash in two patients. CONCLUSIONS Filgrastim is safe and effective in preventing neutropenia and reducing neutropenic treatment interruptions during abdominal radiotherapy in patients with ovarian cancer. However, there was no clear benefit to the use of filgrastim as thrombocytopenia became the dose-limiting toxicity resulting in a risk of treatment interruptions and early termination of radiotherapy.

Heterogeneity in responses to cancer. Part II: Sexual responses.

Heterogeneity in psychosexual responses to disease-specific diagnosis is demonstrated for two groups of cancer patients with testis cancer and Hodgkins disease who are comparable in prognosis and treatment intensity. The two groups of patients and their partners are shown to differ in their ability to recover from psychiatric problems associated with the diagnosis and/or treatment of cancer.

Heterogeneity in responses to cancer. Part I: Psychiatric symptoms.

Heterogeneity in psychiatric responses to disease specific diagnosis is demonstrated for two groups of cancer patients who are comparable in prognosis and treatment intensity. Implications of this heterogeneity are drawn for etiological study and for planning psychiatric interventions.

Large retroperitoneal lymph nodes (RPLN) as a predictor for venous thromboembolism (VTE) in patients (pts) with germ cell tumor (GCT) receiving first-line chemotherapy (chemo).

332 Background: VTE causes significant morbidity and mortality in GCT pts. While an existing and validated predictive model identifies VTE risk in chemo pts with any cancer (Khorana model), a predictive model specific to GCT does not exist. Many GCT pts present with bulky RPLN that produce venous stasis in the lower extremities. The objective of this study was to explore the association between large RPLN and VTE in GCT pts receiving chemo and compare large RPLN as a predictor for VTE in GCT pts to the non-GCT specific Khorana model. METHODS Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy and medical records. All GCT pts receiving 1st line chemo between 1-Jan-00 and 31-Dec-10 were included. Large RPLN were defined as ≥5cm in maximal diameter. Factors used in the Khorana model (baseline BMI, hemoglobin, white cell count and platelets) were collected. We compared the predictive accuracy of large RPLN versus Khorana score ≥3 using receiver operator characteristic (ROC) curve statistical analyses. RESULTS The cohort consisted of 260 GCT pts, median age 31.5 years, predominantly testis primary (235, 90%) and good risk (171, 66%). 17 (7%) developed VTE prior to the start of chemo. 19 (7%) were given prophylactic anticoagulation, none of whom developed VTE. Of the remaining 224 pts, 20 (9%) developed VTE during chemo. In a univariate analysis, large RPLN was strongly associated with VTE (OR 7.74, p<0.001), as were Khorana score ≥3 (OR 9.81, p<0.001) and hospital admission during chemo (OR 3.96, p=0.004). ROC curve analyses demonstrated large RPLN was a significant individual predictor for VTE (AUC 0.588, p=0.03), however, Khorana score ≥3 was a better predictor (AUC 0.664, p=0.02). Adding large RPLN to create a modified Khorana score provided marginal gains (AUC 0.682, p=0.02). CONCLUSIONS Although large RPLN at diagnosis predicts for VTE in GCT pts, the Khorana predictive model is superior. Given the high rate of VTE in GCT pts receiving chemo, we recommend prophylactic anticoagulation for pts at increased risk, including pts with Khorana score ≥3, pts requiring hospital admission or pts with large RPLN.

Impact of renal impairment and granulocyte colony stimulating factor (GCSF) on bleomycin-induced pneumonitis (bleo lung), febrile neutropenia (FN), and survival in patients (pts) with germ cell tumor (GCT) treated with chemotherapy (chemo).

328 Background: Use of GCSF and the development of renal impairment in GCT pts receiving chemo are common, but their effect on toxicity and survival is unclear. This study examines the impact of GCSF and renal impairment on bleo lung, FN and survival, in GCT pts receiving 1st line chemo. METHODS Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy and medical records. All GCT pts receiving 1st line chemo between 1-Jan-00 and 31-Dec-10 were included. Pts receiving at least one GCSF dose were identified. Renal impairment during chemo was defined as any serum creatinine above the institutional upper limit of normal. Bleo lung was graded (G1-5) using CTCAE criteria. FN was defined as temperature ≥38C and neutrophil count <1.0. RESULTS The cohort consisted of 260 GCT pts, median age 31.5 years, 171 (66%) had IGCCCG good risk disease, 42 (16%) intermediate, and 41 (16%) poor, while 6 (2%) received adjuvant chemo. 159 (61%) received GCSF and 49 (19%) developed renal impairment. 212 (82%) received BEP of which 73 (34%) developed bleo lung (56 pts G1 asymptomatic, 13 pts G2, 4 pts ≥G3). Renal impairment was associated with bleo lung in univariate (OR 2.87, p=0.008) and multivariate (OR 2.69, p=0.01) analyses. GCSF was associated with increasing severity of bleo lung (OR 1.86, p=0.045) but this was not significant in a multivariate analysis (OR 1.72, p=0.08). FN occurred in 33 (13%) of 260 pts. Renal impairment (OR 3.91, p=0.001) was associated with FN. Primary GCSF prophylaxis reduced FN (OR 0.26, p=0.001), however, 8 (7%) of 112 patients developed FN in spite of GCSF prophylaxis. Survival analyses demonstrated GCSF and renal impairment did not impact progression free or overall survival (OS), however, bleo lung was associated with poorer OS in a multivariable Cox proportional hazards analysis (HR 2.85, p=0.029). CONCLUSIONS Our findings demonstrate both renal impairment and GCSF are risk factors for bleo lung, while renal impairment itself is also a risk factor for FN. Additionally, we identify bleo lung as a significant poor prognostic factor for OS.

PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION FOR CLINICAL LOW STAGE NONSEMINOMATOUS GERM CELL TESTICULAR TUMORS

498 PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION FOR CLINICAL LOW STAGE NONSEMINOMATOUS GERM CELL TESTICULAR TUMORS David Kakiashvili*, Lynn Anson-Cartwright, Malcolm Moore, Jeremy F G Sturgeon, Alvaro Zuniga, Padraig R Warde, Peter Chung, Justin Liu, Clement Ma, Michael A S Jewett. Toronto, ON, Canada. INTRODUCTION AND OBJECTIVE: Non-risk adapted surveillance is the recommended standard of care for clinical stage I non-seminomatous germ cell testis tumors (NSGCTT) at the Princess Margaret Hospital Testis Tumor Clinic. Primary bilateral retroperitoneal lymph node dissection with sympathetic nerve sparing when feasible (NS-RPLND) is offered as an alternative at patient request and when surveillance is contraindicated. Small volume stage II patients with low marker levels are offered surgery as they usually do not need subsequent chemotherapy. We have evaluated our experience with primary RPLND. METHODS: The charts of the 120 consecutive patients from the Princess Margaret Hospital Testis Tumor Clinic with clinical low stage NSGCTT who underwent primary NS-RPLND between November 1984, when NS was introduced, and October 2007 were reviewed. Adjuvant chemotherapy was offered if resected disease was extensive or pathological characteristics were adverse. Perioperative tumor characteristics, histology, need for additional treatment and functional outcomes, including loss of antegrade ejaculation were assessed. Survival outcomes were generated using the Kaplan-Meier method. RESULTS: The median age at diagnosis was 28.6 years. The median time of follow-up was 4.9 years (0.02 20.89 ). 51 patients (42.5%) were clinical stage I and 69(57.5%) were stage II (61-IIA and 8 IIB). Of those with initial stage I, 20 underwent immediate RPLND and 31 at progression to clinical stage II ( 25 IIA and 6-II B).Outcomes were similar for these groups. Laparotomy revealed grossly enlarged lymph