Annual Meeting Proceedings Part 1 - American Society of Clinical ...

4597 General Poster Session (Board #4D), Sun, 8:00 AM-12:00 PM
Bone metastases in patients with relapsed/refractory germ cell tumors
(GCT) undergoing first salvage chemotherapy: A retrospective analysis of a
large international database. Presenting Author: Karin Oechsle, University
Medical Center Eppendorf, Hamburg, Germany
Background: Bone metastases (mets) are rare events in GCT patients (pts)
and data on characteristics, risk factors, treatment and outcome in these
pts are largely missing. Methods: A subgroup of 104 ptswith bone metsfrom
the IPFSG database was analyzed. All patients experienced unequivocal
relapse/progression after � 3 cycles of cisplatin-based chemotherapy and
received conventional-dose (CDCT) or high-dose salvage chemotherapy
(HDCT). Results: 104 / 1594 pts presented with bone mets (6,5%) at first
relapse. Histology was pure seminoma in 26%, and non-seminoma in 74%.
At initial diagnosis, 54% of pts had presented with �poor risk� according to
IGCCCG. Overall response rate (ORR; CR�PR) to 1st-line chemotherapy
was 89%. Median PFS after primary treatment was 3 months (range 0 -
140). Bone mets at first relapse were accompanied by abdominal, lung,
mediastinal, liver and brain mets in 54%, 48%, 28%, 36%, and 14%,
respectively. Tumor marker profiles were heterogeneous (elevation of AFP /
ß-HCG: 51% / 37%). Salvage treatment was CDCT in 34%, and HDCT in
66% of pts. ORR to salvage chemotherapy was 68% for the total cohort,
and 43% vs. 81% for CDCT vs. HDCT (p�.01). For the total cohort, 2y-PFS
and 5y-OS were 24% and 16%, respectively. 2y-PFS and 5y-OS were
significantly higher in pts after HDCT compared to CDCT (2y-PFS 29% vs.
14%, p�.01; 5y-OS 19% vs. 9%, p�.04). Conclusions: Pts relapsing with
bone mets after platinum-based CTX were characterized by �poor risk�
disease at initial diagnosis, but characteristics at first relapse were
heterogeneous. Treatment response and outcome was improved in pts with
HDCT compared to CDCT. Further prospective evaluation of characteristics
and treatment approaches in GCT pts with bone mets is warranted.
4599 General Poster Session (Board #4F), Sun, 8:00 AM-12:00 PM
Clinical relevance of specialist pathologic testicular tumor review. Presenting
Author: David N. Church, Oxford Cancer Centre, University of Oxford,
Oxford, United Kingdom
Background: Therapeutic options in stage IA/B testicular cancer include
surveillance, retroperitoneal lymph node dissection, and adjuvant chemotherapy/radiotherapy;
clinician and patient choice is guided by recurrence
risk. Specialist pathologic review is important in informing this decision as
it may alter diagnosis and staging. Methods: Analysis of a prospective
supraregional database of 627 testicular tumors diagnosed in Oxford or
referred for central review between 2004 and 2012. Tumor histology, stage
(AJCC 7th ed.), and other factors predictive of relapse were compared
between referring and final pathology reports. Results: Of 402 cases
referred from 11 hospitals during the study period, 370 primary testicular
tumors with an informative initial pathology report were analysed. There
was a discrepancy between referring and final reports in 116 cases
(31.4%), with significant variation between referring units in the frequency
of discordance (20.0-89.9%, p�0.0001, x2 ). Changes to histological
diagnosis in 34 cases (9.2%) were minor alterations in type and proportion
of non-seminomatous germ cell tumor (NSGCT) elements of no clinical
significance, with exception of one classical seminoma reclassified as
spermatocytic seminoma. For seminomas (n�201) the commonest discrepancies
were in identification of rete testis invasion (RTI) (15.9%); lymphovascular
invasion (LVI) (9.5%); and spermatic cord invasion (SCI) (5.0%).
RTI was more frequently under-reported (14.4%), and LVI over-reported
(8.0%) on initial assessment. Disparity of tumor size in 2 cases (1.0%) was
of no clinical significance. For NSGCT (n�150) the commonest discrepancies
were in RTI (9.3%), LVI (7.3%) and SCI (6.7%), with LVI typically
over-reported (4.0%) and RTI and SCI under-reported (6.7%, 5.3%
respectively) on primary analysis. Central review resulted in change of
primary tumor stage in 45 cases (12.1%). 12 (6.0%) and 16 (8.0%)
seminomas, and 12 (8.0%) and 5 (3.3%) NSGCTs were upstaged and
downstaged respectively. Conclusions: Central pathology review results in
frequent alteration of factors predictive of relapse in stage IA/B testicular
cancer. Particular attention should be directed to review of RTI, LVI and
SCI to ensure accurate prognostication.
Genitourinary Cancer
301s
4598 General Poster Session (Board #4E), Sun, 8:00 AM-12:00 PM
Metastatic malignant transformation of teratoma to primitive neuroectodermal
tumor (PNET): Results with PNET-based chemotherapy. Presenting
Author: Amit Jain, Indiana University Melvin and Bren Simon Cancer
Center, Indianapolis, IN
Background: Metastatic germ cell cancers are highly chemosensitive and
have 80% cure rate with cisplatin based chemotherapy. Post-chemotherapy
teratoma can usually be surgically resected. However, teratoma,
which is pleuripotent tissue, can undergo malignant transformation along
mesodermal elements to PNET. Unlike teratoma, PNET can metastasize
and render a patient unresectable and incurable. We report the results of
treatment of patients with PNET with cyclophosphamide � doxorubicin �
vincristine (CAV) alternating with ifosfamide � etoposide (IE). Methods: We
reviewed 81 patients with histologically confirmed PNET transformed from
testicular teratoma at Indiana University from 1998 to 2011. We identified
13 cases who were treated with chemotherapy comprising cyclophosphamide
1000-1200 mg/m2 , doxorubicin 50-75 mg/m2 , and vincristine 2 mg
alternating with ifosfamide 1.8 grams/m2 plus etoposide 100 mg/m2 for 5
days. Treatment was given every 3 weeks with a maximum of 6 cycles or
until progression or undue toxicity. Hematopoeitic growth factors were
usually incorporated. The remaining 68 patients underwent surgical
resection. Results: Ten patients had unresectable disease and 3 were
treated in an adjuvant setting. Median age was 31 years (range 20-53). Ten
of 13 patients had received prior platinum based chemotherapy. Eight of
10 evaluable patients achieved objective response. Five of those were
rendered with no evidence of disease(NED) with further surgery. Although 4
of the 5 patients subsequently relapsed, 1 patient remains alive with NED
at 69 months. The 3 patients who received adjuvant treatment after
retroperitoneal lymph node dissection (RPLND) are alive with NED at 1, 4
and 8 years. Conclusions: CAV and IE alternating chemotherapy has high
objective response rate for PNET transformed from teratoma and results in
occasional long term disease free survival when combined with subsequent
resection. We recommend adjuvant CAV alternating with IE chemotherapy
for patients with PNET after RPLND due to the high probability of recurrent
disease and their high chemosensitivity to this regimen.
4600 General Poster Session (Board #4G), Sun, 8:00 AM-12:00 PM
Quality of life and late toxicities in germ-cell cancer patients after
high-dose chemotherapy. Presenting Author: Thomas Wuendisch, University
Hospital Marburg, Marburg, Germany
Background: The number of long term survivors after treatment for relapsed/
refractory germ cell cancer (GCC) is increasing but little is known about
quality of life (QOL) and late toxicities (LT). Methods: We assessed LT and
QOL in GCC patients (pts), treated in a prospective, randomized, multicenter,
phase III trial comparing single versus sequential high-dose
chemotherapy (HDCT) (Lorch 2007). All 216 pts were asked to complete
the European Organization of Research and Treatment of Cancer Quality of
Life Questionnaire (EORTC QLQ-C30) prior to HDCT, 6 weeks after and
yearly thereafter. Results were analyzed according to standard methods
(Fayers 2001). In addition pts were contacted at a median of 76 months
(range 45-109) after HDCT to obtain information about current social and
professional activities as well as LT. Results: Among 216 pts, 92/216
(42%) were alive and without evidence of disease one year after randomization.
Median age of pts was 34 years (range 15-56). A median of 4
conventional-dose cisplatin-based treatment cycles had been given prior to
HDCT. Questionnaires and response to the survey were evaluable in 86/92
(93%) pts overall and in 59/86 (69%) pts more than 3 years after HDCT.
Values for global health status, role functioning and emotional functioning
declined during the first year after HDCT, increased in the following years,
but did not reach the reference values from large samples of the general
population in Norway (Hjermstad 1998). Pts after sequential HDCT scored
better in a number of items (e.g. emotional-, cognitive-, social-functioning,
fatigue and dyspnoea) in comparison to single HDCT including high-dose
cyclophosphamide. Persisting polyneuropathy was reported in 59%, ototoxicity
or tinnitus in 56%, erectile dysfunction in 24%, hypertension in 23%,
hypercholesterinemia in 17%, diabetes mellitus in 6%, nephrotoxicity in
6%, myocardial infraction in 2% and second cancers in 1% of pts. Overall
82 % of pts were employed, 30% exercised regularly. Conclusions: HDCT
has a negative impact on QOL, including social and professional life. Most
common late toxicities were ototoxicity and polyneuropathy. Sequential
HDCT without cyclophosphamide seems to result in a better outcome in
respect to QOL.
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