HPLC micromethod for simultnaeous measurement of estradiol,progesterone, androgen and glucocorticoid receptor levels. Application to breast cancer biopsies

Estradiol (ER), progesterone (PR), androgen (AR) and glucocorticoid receptor (GR) levels were assayed in 25 breast cancer tumors. The tissue was pulverized and homogenized in buffer, then divided into two parts: one was assayed by the standard dextran-coated charcoal method (DCC), with Scatchard plot analysis, the other was assayed by a micromethod developed in our laboratory, as described below:

• •— incubation of the cytosol with several ligands (labelled and unlabelled) selected to avoid unwanted cross-reactions
• •— DCC separation, followed by extraction of all receptor-bound steroids by precipitation of proteins with methanol/TCA
• •— separation of these steroids on a high pressure liquid chromatography (HPLC) column using a methanol/water solvent
• •— collection of the fractions of the column outlet and counting.

Use of three labelled ligands and appropriate unlabelled ligands allowed assays of the four receptors. This micromethod was highly correlated with the standard method: ER = 0.985 (P < 0.001); PR = 0.999 (P > 0.001); AR = 0.989 (P < 0.001); GR = 0.867 (P < 0.001). Thresholds of positivity were not modified. This micromethod allowed simultaneous measurement of several receptors in 40 mg biopsy specimens and can be applied to other hormone-dependent tissues.     

Hodgkin's disease (HD): A historical perspective

Five hundred and seven patients with Hodgkin's lymphoma (HL), forming the basis of our 18 years experience, are retrospectively analyzed. Four therapeutic periods are recognizable:

• 1.1. The 1966–1970 period was characterized by the absence of treatment and management policy. The 55 patients entered in this period experienced 70 and 56% survival at 5 and 10 yr, respectively, from diagnosis.
• 2.2. The 1971–1974 period was characterized by the increasing knowledge of staging relevance and therapeutic approaches. The 153 patients who were treated in this period experienced 72 and 60% survival and 5 and 10 yr, respectively.
• 3.3. The 1975–1980 period was characterized by a large combination of MOPP and radiotherapy. The 216 patients who entered this period observed 80 and 72.5% survival at 5 and 10 yr, respectively.
• 4.4. The last therapeutic period (1980 to present time) is characterized by the increasing relevance of prognostic factors and alternating use of MOPP and ABVD as non-cross resistant regimen. The 83 patients who entered this period showed 90% survival at 5 yr.

Both survival and disease-free survival were positively influenced by the change of therapeutic strategies during the four periods (P < 0.005). Although better results have been recorded moving from one to the next therapeutic period, the present policy has been also based on the recognition of a high number of late complications due to the therapy. Preliminary results about the present therapeutic experience seem to indicate both a good remission rate and low incidence of complications.     

European Breast Cancer Conference manifesto on breast centres/units

Manifesto—CALL TO ACTION

• •The 2016 deadline for all patients in European Union countries to access specialist, multidisciplinary breast cancer units or centres, will be missed by most countries, despite numerous resolutions and declarations issued since the year 2000 that have called for universal specialist services. This means that many women, and some men, do not receive optimal breast cancer care in Europe.
• •We call on policymakers and politicians to ensure, as soon as possible, that all women and men with breast cancer in Europe are treated in a specialist breast unit.
• To do this, we ask that policymakers and politicians, together with healthcare professionals and patient advocates:
  • -Promote, in public and professional settings, the evidence that breast units staffed with specialist multidisciplinary teams deliver superior care and quality of life to women and men with breast cancer.
  • -Acknowledge the evidence that treatment in multidisciplinary units lead to overall cost savings as well as higher quality of care.
  • -Audit the current national provision of breast cancer care using accredited auditors.
  • -Implement mandatory reimbursement and care models that mean treatment can only be carried out in specialist breast units.
  • -Introduce a breast unit quality certification scheme that is accredited by an accreditation body.
  • -Join European-wide scientific societies and groups that promote the availability and quality of breast units, and together commit to providing access to such units for all patients.

     

Acquired immunodeficiency syndrome-related cancer. A study model for the mechanisms contributing to the genesis of cancer

The study of AIDS and cancer has resulted in an important convergence of clinical–epidemiological investigations, molecular research and virological studies. This shared effort has led to significant discoveries in the field of human carcinogenesis. In a relatively short time, several topics have been clarified, namely:

• &#x02022;The spectrum of AIDS-related tumours has been identified;
• &#x02022;The role of HIV in lymphomagenesis and in the development of Kaposi's sarcoma (KS) has been defined;
• &#x02022;AIDS-related cancers have allowed the discovery and extensive biological characterisation of the novel virus human herpes virus type 8 (HHV8), also called KS-associated herpesvirus;
• &#x02022;Genetic, molecular and phenotypic studies of AIDS-related lymphomas have contributed to the formulation of a pathogenetic and histogenetic model of B-cell non-Hodgkin's lymphomas (NHL).

     

Relation between estrogen receptor concentration and clinical and histological factors: Their relative prognostic importance after radical mastectomy for primary breast cancer

After modified radical mastectomy, 490 primary breast cancer patients were followed for a median of 75 months. Bloom grade was measured in 340 patients and ER status in 341.Follow-up of these patients has yielded the following results:

• (a)The value of traditional indices has been reaffirmed. (Cox's multivariate analysis identified, in order of decreasing importance, the number of invaded lymph nodes, the initial tumor size and the histological grade. Other variables were found to be of lesser importance and were correlated with the three main indices.)
• (b)The value of ER status disappeared after more than 3 years of follow-up.
• (c)ER positive patients fared better after recurrence. This was interpreted as being a consequence of their responsiveness to hormonal treatment.

     

TCNU (LS 2667), a new active drug in the treatment of advanced colorectal cancer

Fifty-seven patients with advanced measurable or evaluable colorectal cancer not previously treated with chemotherapy and tumor manifestations from colorectal cancer were treated with tauromustine (TCNU), a new nitrosourea with a therapeutic index against murine tumors better to or equal to that of the established nitrosoureas. The dose was 130 mg/m² orally q 5 weeks. There were one CR and seven PR, for an overall response rate of 14%. Responding sites included the liver (one CR and two PR), lung (four PR) and lymph nodes (two PR). The median duration of response was 33+ weeks (21+ to 34 weeks). The main dose limiting toxicity was myelosuppression which seemed to be cumulative. Subjectively, the drug was well tolerated although most patients experienced nausea and vomiting for some hours.It is concluded that TCNU is a well tolerated compound with limited, but definite antitumor activity against colorectal cancer and that further studies in this disease could be of interest.     

Nutritional factors and cancers of the breast,endometrium and ovary

From an overview of epidemiological evidence on nutrition, diet and cancers of the breast, endometrium and ovary, the following indications can be drawn:

• •— Overweight and obesity are causally related to endometrial and post-menopausal breast cancer, and may account for as much as one third of the cases of endometrial and one tenth of breast cancer in Europe. It is not known whether obesity or overweight early in life has any role on breast cancer risk, nor whether obesity influences ovarian carcinogenesis. Overweight tends to be associated with an unfavourable prognosis for breast cancer.
• •— Despite extensive research, the available knowledge on diet and breast cancer is largely inconsistent, and the results from ecological and individual-based studies are contradictory in relation to fat, proteins, total energy, alcohol, etc.
• •— There are only scanty data on diet and endometrial or ovarian cancer, which tend to suggest role for fat (or animal fat) in the risk of these neoplasms.
• •— The evidence on diet and breast, ovarian and endometrial carcinogenesis is still too scanty or inconsistent to be of any practical preventive value. Thus, the only clear indication for prevention is that a reduction of overweight would avoid a substantial number of cases of endometrial and post-menopausal breast cancer.

     

Ein einfaches Phantom zur Kalibrierung und Qualitätsüberprüfung von Bestrahlungsplanungssystemen

We developed a simple phantom for the evaluation of treatment planning systems, defined as a unit of 2D- or 3D- planning computers and planning CT's. It enables

• 1he calibration of planning computers and planning CT's with regard to the Hounsfield units
• 2the evaluation of calculation results from planning systems under consideration of density inhomogeneities as they occur in a human body
• 3monthly checks of planning systems under defined and reproducible conditions
• 4the verification of planning system Kernels under inhomogeneous conditions

At present there is no commercially available phantom which could verify calculated data under radiation. Until now these data were checked only under homogeneous conditions (waterphantom, RW3 phantom). Our phantom is easily constructed and provides good and reproducible results. We have compared the data of two planning systems and detected significant discrepancies. The MULTIDATA planning system provided good results. The maximum deviation was approximately 7 %. The data of the PLATO planning system showed a significant deviation of approximately 10–14% with 6MV photons and 15–20% with 15 MV photons. The explanation might be, that the data kernels are not yet sufficiently elaborate and therefore not suitable for clinical use.     

Preclinical phase II studies in human tumor lines: A European multicenter study

In an attempt to increase the predictability and to extend the differential capacity of the anticancer drug development program the American National Cancer Institute has recently proposed the introduction of a screening system consisting of human tumor cell lines to select drugs in a disease-oriented fashion rather than by the previously applied drug-oriented strategy. Although this new approach offers great advantages, assay limitations can be identified in testing unknown compounds for antitumor activity in vitro. Human tumor xenografts grown in nude mice may play an additional role in the prediction of clinical activity and the assessment of the spectrum of activity of potential anticancer drugs, because they have a better relationship with the clinical situation of cancer treatment.In a European multicenter collaboration it has been proposed to use panels of human tumor lines from solid tumor types to study:

• •—the antitumor activity of three different drugs per tumor type;
• •—the reliability of ‘preclinical’ phase II studies by comparison of the obtained data with results of phase II clinical trials;
• •—the feasibility of this joint project, such as the methodology, the reproducibility of experimental data and the introduction of uniform activity criteria.

If preclinical phase II studies in human tumor lines generate reliable results, this in vivo screening system will create a unique possibility to better identify promising clinical candidate compounds or analogs of conventional cytostatic agents as well as those tumor types likely to respond to the selected investigational drugs.     

Combination Therapy with Platinum and Etoposide of Brain Metastases from Breast Carcinoma

Twenty-two consecutive patients with brain metastases from breast carcinoma were treated with a combination of platinum (100 mg/m² day 1) and etoposide (100 mg/m² days 4,6,8) every three weeks. Five (23%) achieved a complete response (CR) while 7 (32%) obtained a partial response (PR) for an overall response rate of 55%. The 95% confidence interval for combined CR and PR was 34-76%. Five patients received brain irradiation after reaching the maximum degree of objective remission by chemotherapy. Median duration of combined CR plus PR was 40 weeks (12 + 152). Median duration of survival was 58 weeks (2; 208+). Fifty-five percent of the patients were alive at one year. Our study demonstrates that this combination treatment is highly effective in the management of brain metastases from breast carcinoma.     

Hairy cell leukemia

BACKGROUND:

Historically, the first treatment choices for hairy cell leukemia (HCL) were splenectomy and alpha‐interferon. Recently, purine analogues (pentostatin and cladribine) changed radically the treatment modality, inducing complete and durable responses in the majority of patients.

METHODS:

The authors analyzed the outcome of different lines of therapy in 121 HCL patients followed in their institute from 1986 to 2008, with a median follow‐up of 105 months. Patients were divided into subgroups according to the number of treatments; Group A included 121 patients who underwent a front‐line therapy, Group B patients (n =53) were treated with 2 lines, Group C patients (n = 34) with 3 lines, Group D patients (n = 17) with 4 lines, and Group E patients (n = 8) with 5 lines.

RESULTS:

In Group A, 92 (77%) patients obtained a complete response (CR), 23 (18%) a partial response, and the remaining 6 (5%) a minor or no response; median duration of response was 2.7 years. In Group B, 53 relapsed patients achieved a second CR rate of 73.5%; median duration of response was 2.5 years. Group C contained 34 patients in a second relapse, with a CR rate after the third line of treatment of 70.5% (median duration of response, 2.2 years). In Group D, 11 (64.7%) patients obtained a CR (median duration of response, 1.6 years), and in Group E 4 (50%) of 8 patients achieved a CR (median duration of response, 1.3 years).

CONCLUSIONS:

This study confirms the high risk (>40% of all patients) of retreatment of HCL patients and the need to maximize primary response. Cancer 2010. © 2010 American Cancer Society.     

Therapeutic Potential of Afatinib in NRG1 Fusion‐Driven Solid Tumors: A Case Series

BackgroundNeuregulin 1 (NRG1) fusions, which activate ErbB signaling, are rare oncogenic drivers in multiple tumor types. Afatinib is a pan‐ErbB family inhibitor that may be an effective treatment for NRG1 fusion‐driven tumors.Patients and MethodsThis report summarizes pertinent details, including best tumor response to treatment, for six patients with metastatic NRG1 fusion‐positive tumors treated with afatinib.ResultsThe six cases include four female and two male patients who ranged in age from 34 to 69 years. Five of the cases are patients with lung cancer, including two patients with invasive mucinous adenocarcinoma and three patients with nonmucinous adenocarcinoma. The sixth case is a patient with colorectal cancer. NRG1 fusion partners for the patients with lung cancer were either CD74 or SDC4. The patient with colorectal cancer harbored a novel POMK‐NRG1 fusion and a KRAS mutation. Two patients received afatinib as first‐ or second‐line therapy, three patients received the drug as third‐ to fifth‐line therapy, and one patient received afatinib as fifteenth‐line therapy. Best response with afatinib was stable disease in two patients (duration up to 16 months when combined with local therapies) and partial response (PR) of >18 months in three patients, including one with ongoing PR after 27 months. The remaining patient had a PR of 5 months with afatinib 40 mg/day, then another 6 months after an increase to 50 mg/day.ConclusionThis report reviews previously published metastatic NRG1 fusion‐positive tumors treated with afatinib and summarizes six previously unpublished cases. The latter include several with a prolonged response to treatment (>18 months), as well as the first report of efficacy in NRG1 fusion‐positive colorectal cancer. This adds to the growing body of evidence suggesting that afatinib can be effective in patients with NRG1 fusion‐positive tumors.Key Points

• NRG1 fusions activate ErbB signaling and have been identified as oncogenic drivers in multiple solid tumor types. Afatinib is a pan‐ErbB family inhibitor authorized for the treatment of advanced non‐small cell lung cancer that may be effective in NRG1 fusion‐driven tumors.
• This report summarizes six previously unpublished cases of NRG1 fusion‐driven cancers treated with afatinib, including five with metastatic lung cancer and one with metastatic colorectal cancer.
• Several patients showed a prolonged response of >18 months with afatinib treatment. This case series adds to the evidence suggesting a potential role for afatinib in this area of unmet medical need.

     

5-azacytidine in acute leukemia.

101 patients with acute leukemia in relapse were treated with 5-azacytidine according to three schedules: Regimen A--300 mg/m2(day divided intravenously at 8 hour intervals for 5 days; Regimen B--750 mg/m2 as a single iv pulse dose administered at 2 to 3 weeks intervals; and Regimen C--300 mg/m2/day by continuous infusion daily for 5 days. Twelve patients achieved a complete remission (CR) and six achieved a partial remission (PR) for an overall 18% response rate. Of 78 patients receiving an adequate trial the response rate was 23%. An average of 1.5 courses and a median of 5 weeks were necessary to achieve a response. The median duration of CR patients was 21 weeks and for PR patients it was 5 weeks. Response rates were 24% for Regimen A, 0 for Regimen B, and 1 of 8 for Regimen C. The CR rate for AML and AMML was 13%. Two of eight AMoL patients achieved a CR. Only 2 of 23 ALL patients responded, one of whom achieved a CR. Toxicity included moderate to severe nausea and vomiting, diarrhea, stomatitis, skin rash, and prolonged myelosuppression. 5-azacytidine has significant activity in the acute nonlymphoblastic leukemias.     

Combination therapy with platinum and etoposide of brain metastases from breast carcinoma

Twenty-two consecutive patients with brain metastases from breast carcinoma were treated with a combination of platinum (100 mg/m2 day 1) and etoposide (100 mg/m2 days 4, 6, 8) every three weeks. Five (23%) achieved a complete response (CR) while 7 (32%) obtained a partial response (PR) for an overall response rate of 55%. The 95% confidence interval for combined CR and PR was 34-76%. Five patients received brain irradiation after reaching the maximum degree of objective remission by chemotherapy. Median duration of combined CR plus PR was 40 weeks (12+; 152). Median duration of survival was 58 weeks (2; 208+). Fifty-five percent of the patients were alive at one year. Our study demonstrates that this combination treatment is highly effective in the management of brain metastases from breast carcinoma.     

Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma

Background:

Both gemcitabine and bexarotene are established single agents for the treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility and efficacy of combining these drugs in a single-arm phase II study.

Methods:

Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy and at least one prior systemic therapy were given four cycles of gemcitabine and concurrent bexarotene for 12 weeks. Responders were continued on bexarotene maintenance until disease progression or unacceptable toxicity.

Results:

The median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although the objective disease response rate at 12 weeks was 31% (partial response (PR) 31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and median overall survival was 21.2 months.

Conclusion:

The overall response rate of the combination did not reach the specified target to proceed further and is lower than that previously reported for gemcitabine as a single agent.     

Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma

BackgroundProgrammed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established.Patients and MethodsThis academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N = 167) or nivolumab (N = 18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia.ResultsMedian time on treatment was 12 months (range 0.7–43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18 months (range 0.7–48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12 months (range 2–23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response.ConclusionsIn this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6 months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients.Clinical trial registrationNCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3)     

Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer

Purpose

This study sought to determine the feasibility and safety of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (5-FU) triple combination chemotherapy (TPF) followed by concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal cancer (NPC).

Methods

Patients with advanced NPC were treated with three cycles of induction chemotherapy. Docetaxel (70 mg/m²) and cisplatin (75 mg/m²) were given on day 1, followed by 5-FU (1,000 mg/m²) as a continuous infusion for 4 days. After induction chemotherapy, cisplatin was given at a dose of 100 mg/m² every 3 weeks with radiotherapy.

Results

Thirty-three patients were enrolled; all patients were stage III (n = 4, 12.1%) or IV (n = 29, 87.9%). Among the patients, 32 patients completed both induction TPF therapy and CCRT, with responses as follows: five patients (15.2%) achieved a complete response (CR), and 27 patients (81.8%) a partial response (PR). At 6 weeks after CCRT, 23 patients (69.7%) had a CR and 9 patients (27.3%) a PR. The 3-year progression-free survival was 75.6% and the 3-year overall survival was 86.1%. Neutropenia (72.7%), febrile neutropenia (9.1%), and nausea (9.1%) were the most severe toxicities (grade 3–4) during induction chemotherapy, and mucositis (39.4%), fatigue (15.2%), and nausea (9.1%) were the most common toxicities (grade 3–4) during CCRT.

Conclusions

Although most patients had stage IV NPC, the TPF induction chemotherapy followed by CCRT showed promising activity with manageable toxicity. These results demonstrated the possibility of effective treatment with the aim of not only a palliative, but also a curative, approach to the treatment of advanced NPC.     

Initial response with methotrexate in advanced head and neck cancer

A prospective non-randomized study was conducted to determine the effectiveness, toxicity and tolerance of Methotrexate (MTX) as initial therapy in patients with advanced head and neck squamous cell carcinoma (H & N Cancer). Eighty patients were given two courses of 100 mg/m2 MTX by i. v. route as abolus at fifteen days interval without Leucovorin rescue. Patients were evaluated for response two weeks after the second course. Response rate was as high as 26.6% CR (Complete Regression) and 42.6% PR (Partial regression) in primary lesion, while it was 8% CR and 42.6% PR in secondaries (regional lymph nodes). This schedule seems to be effective, cheap, well tolerable and can be used on out-patient basis.     

Cis-dichlorodiammineplatinum (Cis-platinum) and etoposide (VP-16) in malignant lymphoma — an effective salvage regimen

Summary Response rates in malignant lymphoma after failure of first-line therapy are generally poor. Twenty-five patients with non-Hodgkin's lymphoma (NHL) unresponsive to standard combination chemotherapy were treated with cis-platinum/VP-16. Alo were heavily pretreated, 29% having received three or more different drug regimens. Seventeen patients were evaluable for response. There were five complete remissions (CR) (29%) and four partial remissions (PR) (24%), giving an overall response rate of 53% (36% of all patients treated). The duration of CR was 12–48 weeks. Median survival for responders was 25 weeks (15–95), compared with only 5 weeks (4–17) for non-responders (P=0.002). Toxicity included nausea and vomiting, alopecia, minor renal impairment, and myelosuppression. This was sometimes severe: WBC<1.0x10⁹/l in three patients (18%) and platelets<50x10⁹/l in five patients (29%). The response rate for this combination is superior to that reported for either cisplatinum or VP-16 alone in similar patients (PR only 26% and 20%–30%, respectively). Further investigation is required to define the role of these drugs in the first-line treatment of poor-prognosis NHL.     

Comparison of RECIST and Choi criteria for computed tomographic response evaluation in patients with advanced gastrointestinal stromal tumor treated with sunitinib

BackgroundControversies exist about computed tomography (CT) response evaluation criteria for patients with gastrointestinal stromal tumor (GIST).Patients and methodsFifty-one patients with advanced GIST treated second line with sunitinib were evaluated with contrast-enhanced CT every 3 months. Response was rated according to RECIST and Choi criteria. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier analysis.ResultsAccording to RECIST, patients were categorized as complete response (CR; n = 0; 0%), partial remission (PR; n = 1; 2.0%), stable disease (SD; n = 37; 72.5%), and progressive disease (PD; n = 13; 25.5%) at 3 months. When Choi criteria were applied responses were CR (n = 0; 0%), PR (n = 16; 31.4%), SD (n = 21; 41.1%), and PD (n = 14; 27.5%). Despite these discrepancies, patients rated as SD with RECIST and PR as well as SD according to Choi criteria displayed similar PFS (41.3, 40.7, and 41.3 weeks, respectively) and OS (100.4, 91.6, and 108.0 weeks, respectively). Patients with PD had significantly shorter PFS (10.1 weeks for both criteria) and OS (29.1 weeks for RECIST; 28.9 weeks for Choi) regardless of the response classification applied.ConclusionIn contrast to absence of progression, discrimination of PR from SD with Choi criteria was of no predictive value.