Research ArticleClinical Studies

Clinicopathological Variables Predictive of Clinical Outcome in Patients with FIGO Stage Ib2-IIb Cervical Cancer Treated with Cisplatin-based Neoadjuvant Chemotherapy Followed by Radical Hysterectomy

ANGIOLO GADDUCCI, GIANCARLO TETI, CECILIA BARSOTTI, ROBERTA TANA, ANTONIO FANUCCHI, CINZIA ORLANDINI, MARIA GRAZIA FABRINI and ANDREA RICCARDO GENAZZANI
Anticancer Research January 2010, 30 (1) 201-208;

Abstract

The aim of this retrospective investigation was to assess the prognostic relevance of some pre-treatment clinical variables and histological findings assessed on the surgical samples of 46 patients with stage Ib2-IIb cervical cancer treated with cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. Seven patients achieved a pathologically documented complete response, 6 had an optimal partial response, 29 had a suboptimal partial response, and 4 had stable disease. As for histological findings on surgical samples, 7 (15.2%) patients had positive lymph nodes, 10 (21.7%) had lymph-vascular space involvement, and 10 (21.7%) had positive parametria and/ or surgical margins. After surgery, 38 patients received further treatment with chemotherapy and/or irradiation. The median follow-up of survivors was 53 months (range, 4-167 months).Thirteen (28.3%) patients developed recurrent tumour, 11 (23.9%) patients died of tumour and one patient died of ictus with no clinical evidence of tumour. Recurrence-free and overall survival were significantly related to tumour stage (Ib2-IIa versus IIb, p=0.01 and p=0.02, respectively), pathologically assessed lymph node status (negative versus positive, p=0.0009 and p=0.007), lymph-vascular space status (negative versus positive, p=0.01 and p=0.009), parametrial and/or surgical margin status (negative versus positive, p=0.0001 and p=0.0005), but not to haemoglobin level before chemotherapy, patient age, tumour grade or chemotherapy regimen. A platelet count before chemotherapy above the median value of 272,000/μl was associated with a trend for a shorter recurrence-free survival (p=0.06) and with a significantly shorter overall survival (p=0.04) when compared with a lower platelet count. In conclusion, FIGO stage, lymph node status, lymph-vascular space status, parametrial and/or surgical margin status and pre-treatment platelet count are predictors of clinical outcome in patients with FIGO stage Ib2-IIb cervical cancer undergoing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. A multivariate analysis on a larger series of homogeneously treated patients is warranted to better define the clinicopathological risk factors useful to adequately plan the therapeutic strategy.

Cervical cancer remains a major health problem worldwide, despite advances in screening, since a relatively high number of cases are in locally advanced stage of disease at presentation (1, 2). Of the 15,081 cervical cancer patients assessed by the International Federation of Gynecology and Obstetrics (FIGO) Annual Report n. 26, 1,275 patients were in stage Ib2, 1,249 in stage IIa, 3,209 in stage IIb, 274 in stage IIIa, 2,946 in stage IIIb, and 472 in stage IVa (2). The standard treatment for locally advanced cervical cancer is represented by cisplatin-based concurrent chemotherapy and external pelvic irradiation followed by brachytherapy (1, 3). A recent meta-analysis of 13 randomised trials on concurrent chemo-radiation in cervical cancer has shown that this treatment modality significantly improved disease-free survival (hazard ratio [HR]=0.78; 95% confidence interval [95% CI]=0.70-0.87, p=0.000005), locoregional recurrence-free survival (HR=0.76; 95% CI=0.68-0.86, p=0.000003), metastasis-free survival (HR=0.81; 95% CI=0.72-0.91, p=0.0004) and overall survival (HR=0.81, 95% CI=0.71-0.91, p=0.0006) compared with irradiation alone, with an absolute gain in 5-year survival of 8%, 9%, 7% and 6%, respectively (4). There was a suggestion of a difference in the survival benefit with tumour stage, not across other patient subgroups. Acute haematological and gastrointestinal toxicity was increased with chemoradiation, whereas data were too sparse for an analysis of late toxicity.

In the last two decades several studies have shown that neoadjuvant chemotherapy followed by radical hysterectomy is able to obtain very satisfactory results in locally advanced cervical cancer (5-11). In particular, the meta-analysis of 5 randomised trials including a total of 872 patients showed that neoadjuvant chemotherapy followed by surgery is superior to irradiation alone in terms of overall survival, with an absolute gain in 5-year overall survival of 14% (from 50% to 64%, HR=0.65, p=0.00004) (7). In an Italian randomised trial, chemo-surgical treatment achieved better progression-free survival (p=0.02) and overall survival (p=0.005) compared with irradiation alone in patients with stage Ib2-IIb disease, whereas there was no significant difference in the clinical outcome between these two treatment modalities in patients with stage III disease (9).

The aim of this retrospective investigation was to assess the prognostic relevance of some pre-treatment clinical variables and histological findings assessed on the surgical samples from patients with stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy followed by radical hysterectomy.

Patients and Methods

This retrospective study was conducted on 46 patients with FIGO stage Ib2-IIb cervical cancer who underwent cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy with pelvic lymphadenectomy at the Department of Gynecology and Obstetrics of the University of Pisa between 1995 and 2009.

Pre-treatment evaluation included history, physical examination, vaginal-pelvic examination, colposcopy, biopsy, complete blood analysis, chest X-ray, and abdominal-pelvic computed tomography [CT] scan. Cystoscopy and/or proctoscopy were performed if there was clinical or CT suspicion of bladder or rectal involvement. Further investigation (i.e. magnetic resonance imaging [MRI], intravenous pyelography, transvaginal and/or transrectal ultrasound) were performed when appropriate.

Physical and vaginal pelvic examination and abdominal-pelvic CT scan were repeated 3-4 weeks after the completion of chemotherapy. All 46 patients underwent radical hysterectomy and pelvic lymphadenectomy within 5-6 weeks after the last cycle of chemotherapy. Clinical responses were determined according to the World Health Organization criteria (12). Pathological responses were retrospectively assessed according to the criteria suggested by Buda et al. (10). Complete response was defined as the complete disappearance of tumour in the cervix with negative lymph nodes; optimal partial response was defined as a persistent residual disease with less than 3 mm stromal invasion including in situ carcinoma on the surgical specimen; and suboptimal response consisted of persistent residual disease with more than 3 mm stromal invasion on the surgical specimen.

Postoperative management was individually established on the basis of histological findings on surgical samples, patient age and general conditions, after an exhaustive discussion with the patient herself. All patients were periodically followed-up with clinical, cytological and radiological examinations until they died or until April 2009. The median follow-up of survivors was 53 months (range, 4-167 months).

Statistical methods. The time from the first cycle of neoadjuvant chemotherapy to the detection of recurrence was defined as recurrence-free survival. The time from the first cycle of neoadjuvant chemotherapy to death or last observation was defined as overall survival. The analysed prognostic variables included patient age, FIGO stage, tumour grade, haemoglobin level and platelet count before chemotherapy, chemotherapy regimen, and pathologically assessed lymph node status, lymph-vascular space status and parametrial and/or surgical margin status.

The statistical package SAS, release 6.7, was used for computations. The cumulative probability of recurrence-free survival and overall survival was estimated by the product-limit method. The log-rank test was used to compare the homogeneity of recurrence-free survival and survival functions across strata defined by categories of prognostic variables.

Results

Patient characteristics at diagnosis and the chemotherapy regimens used are shown in Table I and Table II, respectively.

Patients treated before 1997 received cisplatin in combination with vincristine and bleomycin or with 5-fluorouracil, whereas those treated afterwards usually underwent cisplatin- and paclitaxel-based chemotherapy. The combination of ifosfamide+cisplatin was given to two patients who had a hypersensitivity reaction to paclitaxel. The regimen consisting of epidoxorubicin+paclitaxel+cisplatin was administered to two patients with cervical adenocarcinoma.

All patients completed the planned cycles of chemotherapy and were evaluable for response. Nine (19.5%) patients achieved a clinical complete response, 31 (67.4%) patients had a partial response, 5 (10.9%) patients had stable disease and one (2.2%) patient had progression of disease, for an overall response rate of 86.9%.

All the patients underwent type II-III radical hysterectomy with pelvic lymphadenectomy. Seven patients achieved a pathologically documented complete response, 6 patients had an optimal partial response, 29 patients had a suboptimal partial response, and 4 patients had a stable disease. An optimal pathological response (complete+partial optimal) was obtained in 13 (28.3%) patients.

As for histological findings on surgical samples, 7 (15.2%) patients had positive lymph nodes, 10 (21.7%) patients had lymph-vascular space involvement, and 10 (21.7%) patients had positive parametria and/or surgical margins.

After surgery, 18 patients received additional cycles of consolidation chemotherapy with the induction regimen, 12 underwent concurrent cisplatin-based chemotherapy and external pelvic irradiation with or without brachytherapy, 7 received external pelvic irradiation with or without brachytherapy, one patient underwent 2 cycles of consolidation chemotherapy with the induction regimen followed by external pelvic and para-aortic irradiation, and 8 patients had no further treatment.

View this table:
Table I.

Patient characteristics at diagnosis.

At the time of the present analysis, 13 (28.3%) patients had developed recurrent tumour, 11 (23.9%) patients had died of tumour, and one patient had died of ictus with no clinical evidence of tumour. The site of recurrent disease was the pelvis in 5 patients, para-aortic nodes in 3, the liver in 4, and the pelvis plus liver in one patient.

Recurrence-free survival was significantly related to FIGO stage (Ib2-IIa versus IIb, p=0.01) (Figure 1a), pathologically assessed lymph node status (negative versus positive, p=0.0009) (Figure 2a), lymph-vascular space status (negative versus positive, p=0.01), (Figure 3a), parametrial and/or surgical margin status (negative versus positive, p=0.0001) (Figure 4a), but not to haemoglobin level before chemotherapy (>11.8 g/dl versus ≤11.8 g/dl), patient age (≤47 years versus >47 years), tumour grade (well/moderately differentiated versus poorly differentiated) or chemotherapy regimen (paclitaxel-based versus no-paclitaxel based regimen). There was a trend for a better recurrence-free survival in patients with a pre-chemotherapy platelet count ≤272,000/μl compared with those with a higher platelet count but the difference failed to reach statistical significance (Figure 5a).

At the time of writing, all 9 (100%) patients who achieved a complete clinical response were alive and recurrence free compared with 23 (62.2%) out of 37 who did not (p=0.071). As for pathological response, 12 (92.3%) out of 13 patients who achieved an optimal pathological response were alive and recurrence-free compared with 20 (60.6%) out of 33 who did not (p=0.08).

View this table:
Table II.

Chemotherapy regimens.

Overall survival was significantly related to FIGO stage (Ib2-IIa versus IIb, p=0.02), (Figure 1b), pathologically assessed lymph node status (negative versus positive, p=0.007) (Figure 2b), lymph-vascular space status (negative versus positive, p=0.009) (Figure 3b), parametrial and/or surgical margin status (negative versus positive, p=0.0005) (Figure 4b), platelet count before chemotherapy (≤272,000/μl versus >272,000/μl, p=0.04) (Figure 5b), but not to haemoglobin level before chemotherapy, patient age, tumour grade or chemotherapy regimen.

All 9 (100%) patients who achieved a complete clinical response were alive versus 25 (67.6%) out of 37 who did not (p=0.118). Twelve (92.3%) out of 13 patients who achieved an optimal pathological response were alive versus 22 (66.7%) of the 33 who did not (p=0.158).

Discussion

The role of neoadjuvant chemotherapy in cervical cancer has been much debated in the last two decades. Several pretreatment clinical variables have been found to negatively correlate with the clinical outcome of patients, such advanced FIGO stage (III versus Ib2-IIb) (6,9,10), bulky tumour size (>5 cm versus <5 cm) (5, 6, 9), high tumour grade (6), parametrial involvement (6) and lymph node involvement assessed by diagnostic imaging techniques (9). Similarly, suboptimal pathological response (10,13-15), lymph-vascular space involvement (5), persistent tumour in the parametria (5,6, 14), and metastatic lymph nodes (5, 6, 13,14) at histological examination of surgical samples have been associated with an unfavourable prognosis.

Figure 1.
Figure 1.

a) Recurrence-free survival by FIGO stage. b) Overall survival by FIGO stage.

In the present series, including patients with stage Ib2-IIb cervical cancer undergoing chemotherapy followed by radical surgery, FIGO stage, pathologically assessed lymph node status, lymph-vascular space status, parametrial and/or surgical margin status were significantly related to both recurrence-free survival and overall survival.

The prognostic relevance of pre-treatment platelet count and haemoglobin level in cervical cancer patients undergoing chemo-surgical treatment is still uncertain. Thrombocytosis at diagnosis is a poor prognostic factor for different malignancies, including cervical cancer, probably because it reflects a cascade of biological events correlated with tumour aggressiveness (16-25). Malignant cells often produce cytokines such as interleukin-6 and growth factors able to induce megacaryopoiesis (16, 26-29), and platelets in turn can secrete growth factors able to stimulate cancer cell proliferation, to enhance angiogenesis and to promote metastasis (30-32).

Figure 2.
Figure 2.

a) Recurrence-free survival by lymph-node status. b) Overall survival by lymph-node status.

In a study including 113 women with cervical carcinoma treated with radiotherapy, Hernandez et al. (20) found that 5-year survival was 65% for patients with a pre-treatment platelet count <400,000/μl compared with 25% for those with higher platelet count (p<0.0001) and that thrombocytosis retained prognostic relevance on multivariate analysis (p<0.001). In a Gynecologic Oncology Group [GOG] study on 219 women with stage Ib cervical cancer who underwent radical hysterectomy, 5-year survival was 65% for the patients with a preoperative platelet count >300,000/μl compared with 84% for those with platelet count ≤300,000/μl (p=0.004), and thrombocytosis continued to correlate with poor survival even after adjusting for tumour size, lymph node status, patient age and race (p=0.04) (23). Conversely, in other series, an elevated pre-treatment platelet count was related to poorer recurrence-free survival and overall survival on univariate but not on multivariate analysis (21, 24). In another GOG study including 294 women with stage IIb-IVa disease without para-aortic metastases treated with irradiation and concurrent hydroxyurea or misonidazole, the pretreatment platelet count was not a significant predictor of survival when it was included in the Cox proportional hazard model as a continuous variable (25). However, when the data were stratified dichotomously as platelet count >400,000/μl versus ≤400,000/μl, there was a statistically significant relation to patient survival (risk ratio [RR]=1.55, 95% CI=1.08-2.21). The uncertainties in the literature about the prognostic relevance of the pre-treatment platelet count in cervical cancer may be partly dependent on both the heterogeneity of patient populations regarding tumour stage and treatment modalities, and the differences in the cut-off value for the platelet count chosen for the definition of thrombocytosis.

Figure 3.
Figure 3.

a) Recurrence-free survival by lymph-vascular space status. b) Overall survival by lymph-vascular space status.

Figure 4.
Figure 4.

a) Recurrence-free survival by parametrial and/or surgical margin status. b) Overall survival by parametrial and/or surgical margin status.

Figure 5.
Figure 5.

a) Recurrence-free survival by platelet count before chemotherapy. b) Overall survival by platelet count before chemotherapy.

Anaemia has been reported to be a poor prognostic factor in different malignancies including cervical cancer (33-42). Several investigators have suggested that anaemia at presentation and/or during treatment might heavily impair the clinical outcome of cervical cancer patients undergoing radiotherapy (34, 35, 40) or chemoradiation (36, 38). Few data are currently available as for the prognostic relevance of pre-treatment haemoglobin levels in patients undergoing neoadjuvant chemotherapy (41-43). In a retrospective Italian study on 73 patients with locally advanced cervical cancer treated with platinum-based neoadjuvant chemotherapy, the patients with a pre-treatment haemoglobin level ≥12 mg/dl showed a 5-year survival of 87% compared with 63% for those with a lower haemoglobin level (p=0.008) (42).

In the present series a pre-chemotherapy platelet count above the median value of 272,000/μl was associated with a trend for a shorter recurrence-free survival (p=0.06) and with a significantly shorter overall survival (p=0.04) when compared with a lower platelet count, whereas pre-chemotherapy haemoglobin levels appeared to have no prognostic relevance.

In conclusion, FIGO stage, lymph node status, lymph-vascular space status, parametrial and/or surgical margin status and pre-treatment platelet count are predictors of clinical outcome in patients with FIGO stage Ib2-IIb cervical cancer undergoing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. A multivariate analysis on a larger series of homogeneously treated patients is warranted to better define the clinicopathological risk factors useful to adequately plan the therapeutic strategy.

Footnotes

    • Received July 3, 2009.
    • Revision received November 25, 2009.
    • Accepted November 27, 2009.

References

  1. ↵
    1. Rose PG
    : Chemoradiotherapy: the new standard care for invasive cervical cancer. Drugs 60: 1239-1244, 2000.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Quinn MA,
    2. Benedet JL,
    3. Odicino F,
    4. Maisonneuve P,
    5. Beller U,
    6. Creasman WT,
    7. Heintz APM,
    8. Nyan HYS,
    9. Pecorelli S
    : Carcinoma of the uterine cervix. Int J Gynecol Obstet 95(Suppl 1): S43-104, 2006.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Rose PG
    : Concurrent chemoradiation for locally advanced carcinoma of the cervix: where are we in 2006? Ann Oncol 17(Suppl 10): 224-229, 2006.
    OpenUrl
  4. ↵
    1. Vale C,
    2. Tierney JF,
    3. Stewart LA,
    4. Brady M,
    5. Dinshaw K,
    6. Jakobsen A,
    7. Parmar MK,
    8. Thomas G,
    9. Trimble T,
    10. Alberts DS,
    11. Chen H,
    12. Cikaric S,
    13. Eifel PJ,
    14. Garipagaoglu M,
    15. Keys H,
    16. Kantardzic N,
    17. Lal P,
    18. Lanciano R,
    19. Leborgne F,
    20. Lorvidhaya V,
    21. Onishi H,
    22. Pearcey RG,
    23. Pras E,
    24. Roberts K,
    25. Rose PG,
    26. Thomas G,
    27. Whitney CW
    .Chemoradiotherapy for Cervical Cancer Meta-Analysis. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26: 5802-5812, 2008.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Sardi JE,
    2. Giaroli A,
    3. Sananes C,
    4. Ferreira M,
    5. Soderini A,
    6. Bermudez A,
    7. Snaidas L,
    8. Vighi S,
    9. Gomez Rueda N,
    10. di Paola G
    : Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results.. Gynecol Oncol 67: 61-69, 1997.
    OpenUrlCrossRefPubMed
  6. ↵
    1. Benedetti-Panici P,
    2. Greggi S,
    3. Scambia G,
    4. Amoroso M,
    5. Salerno MG,
    6. Maneschi F,
    7. Cutillo G,
    8. Paratore MP,
    9. Scorpiglione N,
    10. Mancuso S
    : Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Eur J Cancer 34: 341-346, 1998.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Neoadjuvant chemotherapy for cervical cancer meta-analysis collaboration (NACCCMA) collaboration
    : Neoadjuvant chemotherapy for locally advanced cervix cancer. Cochrane Database Syst Rev 2: CD001774, 2004.
    1. González-Martín A,
    2. González-Cortijo L,
    3. Carballo N,
    4. Garcia JF,
    5. Lapuente F,
    6. Rojo A,
    7. Chiva LM
    : The current role of neoadjuvant chemotherapy in the management of cervical carcinoma. Gynecol Oncol 110(3 Suppl 2): S36-40, 2008.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Benedetti-Panici P,
    2. Greggi S,
    3. Colombo A,
    4. Amoroso M,
    5. Smaniotto D,
    6. Giannarelli D,
    7. Amunni G,
    8. Raspagliesi F,
    9. Zola P,
    10. Mangioni C,
    11. Landoni F
    : Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. J Clin Oncol 20: 179-188, 2002.
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Buda A,
    2. Fossati R,
    3. Colombo N,
    4. Fei F,
    5. Floriani I,
    6. Gueli Alletti D,
    7. Katsaros D,
    8. Landoni F,
    9. Lissoni A,
    10. Malzoni C,
    11. Sartori E,
    12. Scollo P,
    13. Torri V,
    14. Zola P,
    15. Mangioni C
    : Randomized trial of neoadjuvant chemotherapy comparing paclitaxel, ifosfamide, and cisplatin with ifosfamide and cisplatin followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the SNAP01 (Studio Neo-Adjuvante Portio) Italian Collaborative Study. J Clin Oncol 23: 4137-4145, 2005.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Lissoni AA,
    2. Colombo N,
    3. Pellegrino A,
    4. Parma G,
    5. Zola P,
    6. Katsaros D,
    7. Chari S,
    8. Buda A,
    9. Landoni F,
    10. Peiretti M,
    11. Dell'anna T,
    12. Fruscio R,
    13. Signorelli M,
    14. Grassi R,
    15. Floriani I,
    16. Fossati R,
    17. Torri V,
    18. Rulli E
    : A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the SNAP-02 Italian Collaborative Study. Ann Oncol 20: 660-665, 2009.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. World Health Organization
    : WHO Handbook for Reporting Results of Cancer Treatment. WHO offset publication No. Geneva, Switzerland, WHO, 1979. http://whqlibdoc.who.int/publications/9241700483.pdf
  13. ↵
    1. Kim DS,
    2. Moon H,
    3. Kim KT,
    4. Hwang YY,
    5. Cho SH,
    6. Kim SR
    : Two-year survival: preoperative adjuvant chemotherapy in the treatment of cervical cancer stages Ib and II with bulky tumor. Gynecol Oncol 33: 225-230, 1989.
    OpenUrlCrossRefPubMed
  14. ↵
    1. Giaroli A,
    2. Sananes C,
    3. Sardi JE,
    4. Maya AG,
    5. Bastardas ML,
    6. Snaidas L,
    7. Rueda NG,
    8. Vighi S,
    9. di Paola GR
    : Lymph node metastases in carcinoma of the cervix uteri: response to neoadjuvant chemotherapy and its impact on survival. Gynecol Oncol 39: 34-39, 1990.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Colombo N,
    2. Gabriele A,
    3. Lissoni A,
    4. Vecchione F,
    5. Zanetta G,
    6. Pellegrino A,
    7. Maneo A,
    8. Floriani I,
    9. Landoni F
    : Neoadjuvant chemotherapy (NACT) in locally advanced uterine cervical cancer (LAUCC): Correlation between pathological response and survival. Proc Am Soc Clin Oncol 17: 352a, (abstr 1359), 1998.
    OpenUrl
  16. ↵
    1. Nashiltz JE,
    2. Yeshurun D,
    3. Eldar S,
    4. Lev LM
    : Diagnosis of cancer-associated vascular disorder. Cancer 77: 1759-1767, 1996.
    OpenUrlCrossRefPubMed
    1. Costantini V,
    2. Zacharski LR,
    3. Moritz TE,
    4. Edwards RL
    : The platelet count in carcinoma of the lung and colon. Thromb Haemost 64: 501-505, 1990.
    OpenUrlPubMed
    1. Bensalah K,
    2. Leray E,
    3. Fergelot P,
    4. Rioux-Leclercq N,
    5. Tostain J,
    6. Guillé F,
    7. Patard JJ
    : Prognostic value of thrombocytosis in renal cell carcinoma. J Urol 175: 859-863, 2006.
    OpenUrlCrossRefPubMed
    1. Scholz HS,
    2. Petru E,
    3. Gücer F,
    4. Haas J,
    5. Tamussino K,
    6. Winter R
    : Preoperative thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer. Anticancer Res 20: 3983-3985, 2000.
    OpenUrlPubMed
  20. ↵
    1. Hernandez E,
    2. Lavine M,
    3. Dunton CJ,
    4. Gracely E,
    5. Parker J
    : Poor prognosis associated with thrombocytosis in patients with cervical cancer. Cancer 69: 2975-2977, 1992.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Lopes A,
    2. Daras V,
    3. Cross PA,
    4. Robertson G,
    5. Beynon G,
    6. Monaghan JM
    : Thrombocytosis as a prognostic factor in women with cervical cancer. Cancer 74: 90-92, 1994 .
    OpenUrlCrossRefPubMed
    1. Rodriguez G
    : Does thrombocytosis have any prognostic significance in cervical cancer? Gynecol Oncol 55: 325-327, 1994.
    OpenUrlPubMed
  23. ↵
    1. Rodriguez GC,
    2. Clarke-Pearson DL,
    3. Soper JT,
    4. Berchuck A,
    5. Synan I,
    6. Dodge RK
    : The negative prognostic implications of thrombocytosis in women with stage IB cervical cancer. Obstet Gynecol 83: 445-448, 1994.
    OpenUrlPubMed
  24. ↵
    1. De Jonge ET,
    2. Viljoen E,
    3. Lindeque BG,
    4. Amant F,
    5. Nesland JM,
    6. Holm R
    : The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and thrombocytosis in stage IB cervical cancer treated by primary radical hysterectomy. Int J Gynecol Cancer 9: 198-205, 1999.
    OpenUrlPubMed
  25. ↵
    1. Hernandez E,
    2. Donohue KA,
    3. Anderson LL,
    4. Heller PB,
    5. Stehman FB
    : The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 78: 137-142, 2000.
    OpenUrlCrossRefPubMed
  26. ↵
    1. Kirnbauer R,
    2. Köck A,
    3. Schwarz T,
    4. Urbanski A,
    5. Krutmann J,
    6. Borth W,
    7. Damm D,
    8. Shipley G,
    9. Ansel JC,
    10. Luger TA
    : IFN-b2, B-cell differentiation factor 2,or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines. J Immunol 142: 1922-1928, 1989.
    OpenUrlAbstract/FREE Full Text
    1. Rawle FC,
    2. Shields J,
    3. Smith SH,
    4. Iliescu V,
    5. Merkenschlager M,
    6. Beverley PC,
    7. Callard RE
    : B cell growth and differentiation induced by supernatants of transformed epithelial cell lines. Eur J Immunol 16: 1017-1019, 1986.
    OpenUrlCrossRefPubMed
    1. Miki S,
    2. Iwano M,
    3. Miki Y,
    4. Yamamoto M,
    5. Tang B,
    6. Yokokawa K,
    7. Sonoda T,
    8. Hirano T,
    9. Kishimoto T
    : Interleukin 6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinoma. FEBS Lett 250: 607-610, 1989.
    OpenUrlCrossRefPubMed
  29. ↵
    1. Verheul HM,
    2. Jorna AS,
    3. Hoekman K,
    4. Broxterman HJ,
    5. Gebbink MF,
    6. Pinedo HM
    : Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets. Blood 96: 4216-4221, 2000.
    OpenUrlAbstract/FREE Full Text
  30. ↵
    1. Munson L,
    2. Upadhyaya NB,
    3. Van Meter S
    : Platelet-derived growth factor promotes endometrial epithelial cell proliferation. Am J Obstet Gynecol 173: 1820-1825, 1995.
    OpenUrlCrossRefPubMed
    1. Featherstone C
    : Aspirin for bowel cancer: an old friend finds a new role. Lancet 350: 418, 1997.
    OpenUrlPubMed
  32. ↵
    1. Salven P,
    2. Orpana A,
    3. Joensuu H
    : Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. Clin Cancer Res 5: 487-491, 1999.
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Dicato M
    : Anemia in cancer: some pathophysiological aspects. Oncologist 8(Suppl 1): 19-21, 2003.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. Grogan M,
    2. Thomas GM,
    3. Melamed I,
    4. Wong FL,
    5. Pearcey RG,
    6. Joseph PK,
    7. Portelance L,
    8. Crook J,
    9. Jones KD
    : The importance of hemoglobin levels during radiotherapy for carcinoma of the cervix. Cancer 86: 1528-1536, 1999.
    OpenUrlCrossRefPubMed
  35. ↵
    1. Dunst J,
    2. Kuhnt T,
    3. Strauss HG,
    4. Krause U,
    5. Pelz T,
    6. Koelbl H,
    7. Haensgen S
    : Anemia in cervical cancers: impact on survival, patterns of relapse, and association with hypoxia and angiogenesis. Int J Radiat Oncol Biol Phys 56: 778-787, 2003.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Obermair A,
    2. Cheuk R,
    3. Horwood K,
    4. Neudorfer M,
    5. Janda M,
    6. Giannis G,
    7. Nicklin JL,
    8. Perrin LC,
    9. Crandon AJ
    : Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: Effect on progression-free survival. Int J Gynecol Cancer 13: 633-639, 2003.
    OpenUrlPubMed
    1. Cho EI,
    2. Sasaki CT,
    3. Haffty BG
    : Prognostic significance of pretreatment hemoglobin for local control and overall survival in T1-T2N0 larynx cancer treated with external beam radiotherapy. Int J Radiat Oncol Biol Phys 58: 1135-1140, 2004.
    OpenUrlCrossRefPubMed
  38. ↵
    1. Winter WE 3rd,
    2. Maxwell GL,
    3. Tian C,
    4. Sobel E,
    5. Rose GS,
    6. Thomas G,
    7. Carlson JW
    : Association of hemoglobin level with survival in cervical carcinoma patients treated with concurrent cisplatin and radiotherapy: a Gynecologic Oncology Group Study. Gynecol Oncol 94: 495-501, 2004.
    OpenUrlCrossRefPubMed
    1. Gadducci A,
    2. Sartori E,
    3. Landoni F,
    4. Zola P,
    5. Maggino T,
    6. Colombo N,
    7. Fanucchi A,
    8. Chiudinelli F,
    9. Lapresa M,
    10. Maria Ferrero A
    : Pre-chemotherapy hemoglobin levels and survival in patients with advanced epithelial ovarian cancer who received a first-line taxane/platinum-based regimen: results of a multicenter retrospective Italian study. Gynecol Oncol 98: 118-123, 2005.
    OpenUrlCrossRefPubMed
  40. ↵
    1. Serkies K,
    2. Badzio A,
    3. Jassem J
    : Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy. Acta Oncol 45: 695-701, 2006.
    OpenUrlPubMed
  41. ↵
    1. Van Belle SJ,
    2. Cocquyt V
    : Impact of haemoglobin levels on the outcome of cancers treated with chemotherapy. Crit Rev Oncol Hematol 47: 1-11, 2003.
    OpenUrlCrossRefPubMed
  42. ↵
    1. Fuso L,
    2. Mazzola S,
    3. Marocco F,
    4. Ferrero A,
    5. Dompè D,
    6. Carus AP,
    7. Zola P
    : Pretreatment serum hemoglobin level as a predictive factor of response to neoadjuvant chemotherapy in patients with locally advanced squamous cervical carcinoma: a preliminary report. Gynecol Oncol 99(Suppl 1): S187-191, 2005.
    OpenUrlPubMed
  43. ↵
    1. Bellati F,
    2. Pernice M,
    3. Manci N,
    4. Palaia I,
    5. Tomao F,
    6. Marchetti C,
    7. Zullo MA,
    8. Muzii L,
    9. Angioli R,
    10. Benedetti Panici P
    : Hemoglobin variation and blood transfusion rates in patients affected by locally advanced cervical cancer undergoing neoadjuvant chemotherapy followed by radical surgery: the role of erythropoietic growth factors. Ann Oncol 18: 722-729, 2007.
    OpenUrlAbstract/FREE Full Text
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Clinicopathological Variables Predictive of Clinical Outcome in Patients with FIGO Stage Ib2-IIb Cervical Cancer Treated with Cisplatin-based Neoadjuvant Chemotherapy Followed by Radical Hysterectomy
ANGIOLO GADDUCCI, GIANCARLO TETI, CECILIA BARSOTTI, ROBERTA TANA, ANTONIO FANUCCHI, CINZIA ORLANDINI, MARIA GRAZIA FABRINI, ANDREA RICCARDO GENAZZANI
Anticancer Research Jan 2010, 30 (1) 201-208;
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