1. Journal Club
• Continuous Infusion, and Concurrent
Radiotherapy in Patients With Locally
Advanced Esophageal Cancer Produced a
High Percentage of Long-Lasting Pathological
Complete Response
• Cancer. 2012 Nov 16;[Epub Ahead of Print], F
Pasini, G de Manzoni, A Zanoni, et al

2. Background
• This phase 2 study was aimed at defining the
pathological response rate of a neoadjuvant
schedule including weekly docetaxel and
cisplatin, continuous infusion (c.i.) of 5-
fluorouracil (5-FU) and concomitant
radiotherapy (RT) in untreated stage II-III
adenocarcinoma and squamous cell
carcinoma of mid-distal thoracic esophagus.

3. Methods
• The schedule consisted of a first phase of
chemotherapy alone and of a second phase of
concurrent chemoradiation. Doses were as
follows: docetaxel 35 mg/m2 and cisplatin 25
mg/m2 on days 1, 8, 15, 29, 36, 43, 50, and 57
plus 5-FU c.i. (180 mg/m2 on days 1-21 and
150 mg/m2 on days 29-63); RT (50 Gy) started
at day 29. Surgery was planned 6 to 8 weeks
after the completion of chemoradiation.

4. Results
• A total of 74 patients were enrolled;
pathological complete remission (pCR) was
found in 47% (35 of 74) and near pCR
(microfoci of tumor cells on the primary tumor
without lymph nodal metastases) (pnCR) in
15% of the patients (11 of 74). Grade 3-4
neutropenia, nonhematological toxicity, and
toxic deaths occurred in 13.5%, 32.4%, and 4%
of the patients, respectively.

5. Results
• Median follow-up was 55 months (range, 3-
108 months). Median survival of all 74
patients was 55 months, whereas it was not
reached in the pCR subset.
• The 3- and 5-year survival rates were,
respectively, 83% and 77% for pCR, 73% and
44% for pnCR, and 21% and 14% for Residual
Tumor subsets (P < .001).

6. Conclusion
• This study shows that 1) this intensive weekly
schedule produced a high pathological
response rate, 2) responders had high and
long-term durable survival rates.

7. • Lapatinib Plus Capecitabine in Patients With
Previously Untreated Brain Metastases from
HER2-positive Metastatic Breast Cancer
(LANDSCAPE): A Single-group Phase 2 Study
• Lancet Oncol. 2012 Nov 1;[Epub Ahead of
Print], T Bachelot, G Romieu, M Campone, et
al

8. Background
• Brain metastases occur in 30–50% of patients
with metastatic HER2-positive breast cancer.
• In the case of diffuse brain metastases,
treatment is based on whole brain radiotherapy
(WBRT).
• Few systemic options are available. We aimed to
investigate the combination of lapatinib plus
capecitabine for the treatment of previously
untreated brain metastases from HER2-positive
breast cancer.

9. Methods
In this single-arm phase 2, open-label,
multicentre study, eligible patients had HER2-
positive metastatic breast cancer with brain
metastases not previously treated with WBRT,
capecitabine, or lapatinib.
• Treatment was given in 21 day cycles:
patients received lapatinib (1250 mg, orally)
every day and capecitabine (2000 mg/m2,
orally) from day 1 to day 14

10. Methods
• The primary endpoint was the proportion of
patients with an objective CNS response,
defined as a 50% or greater volumetric
reduction of CNS lesions in the absence of
increased steroid use, progressive neurological
symptoms, and progressive extra-CNS disease.
All responses had to be confirmed 4 weeks
after initial response. Efficacy analyses
included all patients who received the study
drugs and were assessable for efficacy criteria.

11. Results
Between April 15, 2009, to Aug 2, 2010, we
enrolled 45 patients, 44 (98%) of whom were
assessable for efficacy, with a median follow-
up of 21.2 months (range 2.2–27.6). 29
patients had an objective CNS response
(65.9%, 95% CI 50.1–79.5); all were partial
responses.

12. Results
• Of all 45 treated patients, 22 (49%) had grade
3 or grade 4 treatment-related adverse
events, of which the most common were
diarrhoea in nine (20%) patients and hand-
foot syndrome in nine (20%) patients. 14
(31%) patients had at least one severe adverse
event; treatment was discontinued because of
toxicity in four patients. No toxic deaths
occurred.

13. Interpretation
• The combination of lapatinib and capecitabine
is active as first-line treatment of brain
metastases from HER2-positive breast cancer.
A phase 3 trial is warranted.

14. • Benefit of Adjuvant Trastuzumab-Based
Chemotherapy in T1ab Node-Negative HER2-
Overexpressing Breast Carcinomas: A
Multicenter Retrospective Series
• Ann Oncol. 2012 Oct 26;[Epub Ahead of Print],
MJ Rodrigues, J Peron, J-S Frenel, et al

15. Background
• Randomized clinical trials showed the benefit
of adjuvant trastuzumab-based chemotherapy
(ATBC) for node-positive and/or >1 cm HER2+
breast carcinomas. No efficacy data have been
published on ATBC in large series of pT1abN0
HER2+ tumors.

16. Patients and Methods
• This retrospective study evaluated 276 cases
of pT1abN0 HER2+ breast tumors in eight
French cancer centers. Factors associated with
prognosis and ATBC prescription were
analyzed.

17. Results
• A total of 129 cases (47%) were treated with
ATBC (ATBC+), 19 with chemotherapy alone, 5
with trastuzumab alone, and 123 (45%) with
neither trastuzumab nor chemotherapy
(ATBC−). ATBC use was associated with the
date of diagnosis (before or after June 2005)
and with poor prognostic features. At a
median follow-up of 44 months, there were
13 recurrences in the ATBC− group and 2 in
the ATBC+ group. A

18. Results
• ATBC was associated with a significant
survival benefit (99% 40-month disease-free
survival for ATBC+ versus 93% for ATBC− cases;
P = 0.018).
• Lack of hormone receptors (HRs) and the
presence of lymphovascular invasion (LVI)
were significantly associated with a poor
prognosis and a greater benefit of ATBC

19. Conclusions
• ATBC was associated with a significantly
reduced risk of recurrence in pT1abN0 HER2+
tumors, and was more beneficial in HR−
and/or LVI+ tumors.

20. • Neoadjuvant Chemoradiotherapy for Patients
With High-Risk Extremity and Truncal
Sarcomas: A 10-year Single Institution
Retrospective Study
• Eur J Cancer. 2012 Oct 22;[Epub Ahead of
Print], NJ Look Hook, FJ Hornicek, DC Harmon,
et al

21. Background
• Patients with large, high-grade extremity and
truncal soft tissue sarcomas (STS) are at
considerable risk for recurrence. A regimen of
pre-operative chemotherapy consisting of mesna,
adriamycin, ifosfamide and dacarbazine (MAID),
interdigitated with radiotherapy (RT), followed by
resection and post-operative chemotherapy with
or without RT, has demonstrated high rates of
local and distant control. The goal of this study is
to assess outcomes in a recent cohort of patients
treated on this regimen.

22. Methodss
We retrospectively reviewed records of 66
consecutive patients with STS of the extremity
or trunk who were treated with the
aforementioned regimen from May 2000 to
April 2011. Clinicopathologic characteristics
and patient outcomes were analysed.

23. Fig. 1
Source: European Journal of Cancer (DOI:10.1016/j.ejca.2012.10.002 )
Terms and Conditions

24. Results: Sixty-six patients were analysed and were equally
divided between grade 2 and 3 tumours. Margins were
negative in 57 (89%) patients and positive in seven (11%)
patients. At a median follow-up of 46months, there were six
(9%) locoregional and 20 (30%) distant recurrences. The
locoregional and distant 5-year recurrence-free survival
(RFS) rates were 91% and 64%, respectively. The 5-year
overall (OS) and disease-specific survival rates

25. The 5-year overall (OS) and disease-specific
survival rates were 86% and 89%, respectively.
There were no treatment-related deaths or
secondary myelodysplasias. Thirty-four (52%)
patients had grade 3 or 4 acute haematologic
chemotherapy-related toxicity. There were no
statistically significant predictors of OS or RFS.

26. Conclusions: For a contemporary cohort of
patients with high-risk extremity and truncal
STS, a regimen of neoadjuvant
chemoradiotherapy and surgery continues to
result in high rates of survival with tolerable
short- and long-term toxicity.

27. • Randomized Trial of Short-Course
Radiotherapy Versus Long-Course
Chemoradiation Comparing Rates of Local
Recurrence in Patients With T3 Rectal Cancer:
Trans-Tasman Radiation Oncology Group Trial
01.04
• J Clin Oncol. 2012 Sept 24;[Epub Ahead of
Print], SY Ngan, B Burmeister, RJ Fisher, et al

28. • It is well established that adding radiotherapy to
surgery has been shown to improve local control
of rectal cancer. Short-course (SC) preoperative
radiotherapy has demonstrated effectiveness
over a long period in tumor control. More
recently, long-course (LC) preoperative
radiotherapy has demonstrated increased
effectiveness in terms of local tumor control. Still,
there is debate among clinicians about which
approach provides better tumor control.

29. • The Trans-Tasman Radiation Oncology Group Trial
01.04 included 323 patients with clinical stage T3 rectal
cancer who were randomly assigned to receive SC or LC
preoperative radiotherapy. The median potential
follow-up time was 5.9 years. The cumulative incidence
of local tumor recurrence at 3 years was 7.5% for the
SC group and 4.4% for the LC group (95% CI, –2.1%–
8.3%; P = .24). The investigators noted that the risk of
local tumor recurrence was lower for patients receiving
LC but not statistically significant (hazard ratio for
LC:SC, 0.75; 95% CI, 0.32–1.77; P = .66).

30. • It should be noted that 93 patients experienced a
distant tumor recurrence either as a first or subsequent
recurrence. The 5-year cumulative incidence rate of
distant tumor recurrence was 27% for patients in the
SC group and 30% for those in the LC group. In regard
to distal tumors, there was a large (but not statistically
significant) difference between treatments with
respect to risk of local tumor recurrence, with 6 of 48
patients receiving SC and 1 of 31 patients receiving LC
experiencing local tumor recurrence (hazard ratio for
LC:SC, 0.26; 95% CI, 0.06–1.20; P = .26).

31. • Of interest, there was no difference
demonstrated in overall survival (OS) between
patients receiving SC and LC preoperative
radiotherapy (5-year OS rates: SC group, 74%;
LC group, 70%; hazard ratio for LC:SC, 1.12;
95% CI, 0.76–1.67; P = .62).

32. Epithelioid Sarcoma
• Epithelioid sarcoma is a rare sarcoma that affects young adults with
an affinity to the distal upper extremity (hand and forearm). It
mostly starts as a painless slow growing mass, but not uncommonly
presents as a multifocal lesion. It has a high tendency for recurrence
and spread along lymphatic channels. Biopsy is the diagnostic
method of choice, with nodular, "pseudoganulomatous" formation
with polygonal cells blended with spindle cells as the most common
pattern seen microscopically. Loss of INI1 gene has been
documented in majority of epithelioid sarcomas and may be used
to confirm the diagnosis. Treatment primarily consists of wide
resection. The role of adjuvants is debated. Male sex, tumor size
more than 2 cm, proximal tumors and presence of vascular invasion
in the microscopic specimen are correlated with worse clinical
outcome.