PubMed HealthSearch

Biomedical subjects

J Dunst

Publications and source records attributed to J Dunst.

At least 19 recordsLinked to original sources

Influence of the hypoxic subvolume on the survival of patients with head and neck cancer.

PURPOSE: Tumor hypoxia is regarded as an important factor influencing radiation response, disease-free, and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN). This study was performed to reevaluate the prognostic significance of the "classical oxygenation parameters" hypoxic fraction (percentage of pO2 values < 5 mmHg or < 2.5 mmHg, respectively) and median pO2, and to determine the influence of a new radiobiological factor. This factor was termed the "hypoxic subvolume" (HSV) and was defined as percentage of pO2-values below 5 mmHg multiplied by the total tumor volume. The rationale of this parameter was to quantify approximately the amount of hypoxic tissue which should be correlated to the number of hypoxic cells in the tumor. It is obvious that a tumor of 100 cm3 with a hypoxic fraction of 20% (HSV = 20 cm3) contains more hypoxic cells than a tumor of 1 cm3 with a hypoxic fraction of 50% (HSV = 0.5 cm3). METHODS AND MATERIALS: Pretreatment pO2 was assessed in 59 patients with SCCHN with the Eppendorf histograph, and pretreatment volume was determined by ultrasonography (lymphnode metastases) and computer tomography (primaries). All patients were referred to our departments for radiotherapy (n = 27, median dose 70 Gy) or radiochemotherapy (n = 32; 5-FU, mitomycin C, median dose 70 Gy), respectively. All parameters were evaluated using the Kaplan-Meier analysis, and significance was assumed at a p-value of < 0.05 (log-rank test, Cox-Mantel). A multivariate analysis was performed to control for confounding factors. The median follow-up was 233 days. At the time of the evaluation, 34 of the 59 patients were dead. RESULTS: In univariate analyses, the hypoxic fraction (pO2 < 5 mmHg, PO2 < 2.5 mmHg [p < 0.05]), the hemoglobin concentration (p < 0.05), and the hypoxic subvolume (p < 0.01) were of prognostic significance for overall survival. In multivariate analysis, the hemoglobin concentration and the hypoxic subvolume (p = 0.01) were significant prognosticators. We found no significant correlation between tumor volume or median pO2 and overall survival. No clear correlation was found between tumor volume and hypoxic fraction. CONCLUSION: These data suggest that the total amount of hypoxic tissue, as determined by the hypoxic subvolume, influences the prognosis of patients suffering from SCCHN. In addition, our data confirm the statements of previous studies that low pretherapy pO2-values indicate a worse prognosis.

Analysis of Variance

Pelvic Ewing sarcoma: a retrospective analysis of 241 cases.

BACKGROUND: This article reports on 241 patients each with pelvic Ewing sarcoma registered for studies in Germany, Austria, and the Netherlands from January 1, 1981, until January 31, 1994. One hundred sixty-four patients had localized disease and 87 had metastases at diagnosis (PMP). Eighty-four patients with localized disease were entered on protocol (PP) and 80 were followed (FP). METHODS: Statistics included an analysis of event free survival by the Kaplan-Meier method and a Cox regression analysis of factors influencing prognosis. RESULTS: In the Kaplan-Meier analysis, on February 1, 1995, the event free survival (EFS) rate was 32% at 12 years for all patients, 54% for PP, 25% for FP, and 13% for PMP. Cox regression analysis showed that response to chemotherapy, initial metastases, and less intense therapy were significant prognostic factors. Among patients who had surgery for local control, the histologic response to chemotherapy was analyzed in the surgical specimen and had a significant influence on survival: EFS 69% for PP with good response compared with 47% (P = 0.11) for patients with poor response, and for FP 56% versus 13% (P = 0.002). All PP with small tumors had relapse free survival, compared with 69% of patients with medium-sized tumors and 36% of patients with tumors larger than 200 mL (P = 0.006). The initial tumor volume was a significant predictor of survival. CONCLUSIONS: Combined modality treatment has resulted in definitive improvement of prognosis for patients with localized pelvic Ewing sarcoma. However, the results for patients with metastases at diagnosis are still discouraging, and their treatment requires new approaches. Tumor load, responsiveness to chemotherapy, and adequate surgical margins are the major factors influencing the prognosis of patients with localized Ewing sarcoma of the pelvis.

Adolescent

Oxygenation of cervical cancers during radiotherapy and radiotherapy + cis-retinoic acid/interferon.

PURPOSE: We have evaluated the tumor tissue pO2 in cervical cancers during radiotherapy with special emphasis on the course of the pO2 in primarily hypoxic tumors and in patients treated with radiotherapy plus 13-cis-retinoic acid/interferon-alpha-2a. METHODS AND MATERIALS: From June 1995 through April 1997, 49 patients with squamous cell carcinoma FIGO IIB-IVA of the cervix who were treated with definitive radiotherapy with curative intent underwent polarographic measurement of tumor tissue pO2 with an Eppendorf pO2-histograph prior to and during radiation treatment. Radiotherapy consisted of external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus high dose rate (HDR) brachytherapy. Twenty-two patients had additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) and interferon-alpha-2a (IFN-alpha-2a). Therapy with cRA/IFN in these patients started 2 weeks before radiotherapy; during this induction period, cRA was administered in a dosage of 1 mg per kilogram body weight orally daily and IFN-alpha-2a in a dosage of 6x10(6) I.U. subcutaneously daily. After start of external radiotherapy (XRT), cRA/IFN was continued concomitantly with radiotherapy in reduced doses (0.5 mg cRA per kg body weight orally daily plus 3x10(6) I.U. IFN-alpha-2a subcutaneously three times weekly until the end of the radiation treatment). PO2 measurements were performed prior to radiotherapy, at 20 Gy, and at the end of radiotherapy. RESULTS: A poor oxygenation defined as a median pO2 of 10 mm Hg or less was present in 15/38 tumors (39%) in which measurements prior to any treatment were done. Low pO2 readings below 5 mm Hg were present in 70% of all tumors prior to treatment. In 13 of 15 hypoxic tumors, pO2 measurements at 19.8 Gy were performed. In these tumors, a significant increase of the median pO2 from 6.0+/-3.1 mm Hg to 20.7+/-21.2 mm Hg was found, p<0.01. The increase in the median pO2 was more pronounced in patients with radiotherapy plus additional cRA/IFN treatment as compared to patients treated with irradiation alone (median pO2 raised from 7.0+/-3.5 mm Hg to 40.9+/-21.3 mm Hg versus 5.7+/-3.1 mm Hg to 14.7+/-17.9 mm Hg). In a multivariate analysis, both the effect of radiation dose (pretreatment versus 19.8 Gy) and the type of treatment (XRT alone versus XRT plus cRA/IFN) had significant impact on the pO2 (P = 0.003 and p = 0.04). In patients with well-oxygenated tumors (pretreatment median pO2>10 mm Hg), 20/23 (87%) achieved a clinically complete response. In patients with primarily hypoxic tumors, 6/6 patients whose primarily hypoxic tumors showed an increase of the median pO2 above 10 mm Hg at 19.8 Gy achieved a complete remission (CR). In contrast, only 4/7 patients with a low pretreatment and persisting low median pO2 achieved a CR. CONCLUSIONS: There are evident changes in the oxygenation of cervical cancers during a course of fractionated radiotherapy. In primarily hypoxic tumors, a significant increase of the median pO2 was found. An additional treatment with cis-retinoic acid/interferon further improved the oxygenation. An impact of the different patterns of oxygenation on local control is to be evaluated.

Adult

Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for localized Ewing sarcoma of bone: the CESS 86 experience. Cooperative Ewing Sarcoma Study.

BACKGROUND: The Cooperative Ewing Sarcoma Study (CESS 86), conducted by the German Society of Pediatric Oncology and Hematology (GPOH), was planned on the basis of the results of the preceding CESS 81 study. The prognostic significance of tumor volume in localized Ewing sarcoma of bone was well documented in the CESS 81 trial. As a consequence, the treatment intensity was adapted to volume in the follow-up CESS 86 trial: the four-drug combination used in CESS 81 was amended for patients with large tumor volume (> or = 100 ml), where ifosfamide was substituted for cyclophosphamide. PROCEDURE: From January 1986 to June 1991, 177 protocol patients with localized Ewing sarcoma of bone were registered in CESS 86. The prognostic implication of tumor volume and several covariates was evaluated using Kaplan-Meier life table analysis and Cox's proportional hazard model. RESULTS: The estimated 5- and 8-year event-free survival (EFS) rates were both 59%. Age, gender, tumor site, and a tumor volume of 100 ml did not distinguish groups of patients with different prognosis. However, the prognosis of patients with tumors >200 ml (8-year EFS rate: 42%) was significantly inferior compared to patients with tumors both of 100 to 200 ml (70%) and of <100 ml (63%). In contrast to CESS 81, the histological response to chemotherapy was no longer a significant prognostic factor (EFS: 64% for good and 50% for poor responders, respectively). CONCLUSIONS: Despite risk-adapted treatment intensity, tumor volume retained its prognostic significance; the cut point, however, was shifted toward larger volumes.

Adolescent

Low hemoglobin is associated with increased serum levels of vascular endothelial growth factor (VEGF) in cancer patients. Does anemia stimulate angiogenesis?

BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell specific mitogen with strong angiogenic activity. Expression of VEGF may therefore be an indicator for the angiogenic potential and biological aggressiveness of a tumor. Recently, measurement of the VEGF-protein in sera has become available. We report results of serum-VEGF in an unselected group of patients with cancer with special emphasis on a possible role of anemia. PATIENTS AND METHODS: Between August 1997 and January 1998, serum-levels of VEGF were determined in a total number of 54 consecutive patients with previously untreated, non-metastatic carcinomas at the Department of Radiotherapy at the Martin-Luther University Halle-Wittenberg. The age ranged from 35 through 89 years with a median age of 67 years. All patients had locoregional confined disease without evidence of hematogenous metastases. Tumor sites were gynecological cancers in 22, head and neck in 14, gastrointestinal in 13, lung in 4 and prostate in 1 case. Forty-four patients had squamous carcinomas and 10 adenocarcinomas. Prior to treatment, routine laboratory work-up was done including measurement of serum-vascular endothelial growth factor (VEGF). The pretreatment hemoglobin ranged from 8.9 through 15.6 g/dl with a median of 13 g/dl. VEGF was measured with a quantitative sandwich enzyme immunoassay technique. RESULTS: The serum levels of VEGF in 40 patients with benign diseases ranged from 57 through 891 pg/ml with a mean of 267 +/- 170 pg/ml. In the investigated 54 cancer patients, VEGF ranged from 62 through 2,609 pg/ml with a mean of 614 +/- 551 pg/ml. Age, UICC/FIGO-stage, T- or N-category, primary tumor site, grade and histologic type had no significant impact on VEGF-serum levels. There was, however, an association between hemoglobin level and serum-VEGF with an increased mean serum-VEGF in 26 patients with a low hemoglobin (< 13 g/dl) as compared to 28 patients with a hemoglobin > 13 g/dl (805 +/- 656 vs 438 +/- 360, p = 0.016, 2-sided t-test). CONCLUSIONS: With regard to the recently established correlation between anemia and intratumoral hypoxia, the increased serum-VEGF levels in patients with low hemoglobin may be explained via hypoxia-induced VEGF secretion. This would suggest that anemia may stimulate angiogenesis via hypoxia. The hypothesis, however, requires further investigation and might have important therapeutical impact.

Adenocarcinoma

Preliminary results of simultaneous radiochemotherapy with paclitaxel for urinary bladder cancer.

BACKGROUND: Paclitaxel (Taxol) has been shown to be effective in metastatic bladder cancer as single agent and in combination with other cytotoxic drugs. Its efficacy seems to be comparable to cisplatin. We have used paclitaxel as alternative to cisplatin in selected patients with simultaneous radiochemotherapy. The objective of this article is to summarize the preliminary results with regard to feasibility and toxicity. PATIENTS AND METHODS: From 10/97 through 10/98 7 patients with locally advanced or recurrent urothelial bladder cancer were treated with radiotherapy and simultaneous paclitaxel + cisplatin. All patients had macroscopic irresectable residual tumor after transurethral surgery or cystectomy. Paclitaxel was given twice weekly in a daily dosage of 25 through 35 mg/m2 as 1-hour-infusion. Cisplatin was given in a dosage of 25 mg/m2 daily on days 1 to 5. RESULTS: All patients completed the scheduled therapy regimen. The acute toxicity consisted mainly of enteritis (Grade I to II CTC). As severe toxicity, 1 severe skin reaction in the groins (Grade III) after 20 Gy and 1 Grade-III enteritis were noted. Both patients with severe complications recovered within 4 weeks after treatment. Hematological toxicity was mild to moderate in all cases. CONCLUSIONS: This report suggests that paclitaxel is a promising agent for simultaneous radiochemotherapy protocols. The clinical value remains to be better defined especially the question whether paclitaxel may improve the results if used as alternative to standard cisplatin. At the moment paclitaxel offers at least an attractive alternative to cisplatin in patients with impaired renal function.

Adult

[Postoperative radiotherapy in endometrial carcinoma. A retrospective analysis of 541 cases].

PURPOSE: This retrospective study was designed to evaluate the role of adjuvant radiotherapy for surgically treated endometrial carcinoma. PATIENTS AND METHODS: From 1980 through 1988, 541 patients were treated with either intravaginal cuff irradiation with a high-dose-rate (HDR) Iridium-192 remote afterloading technique (n = 294) or with combined HDR-brachytherapy and additional external pelvic irradiation to 54 Gy (n = 247) after surgery for endometrial cancer. Afterloading irradiation was administered in 4 fractions 4 to 6 weeks after surgery. A dose of 30 Gy was delivered at a depth of 0.5 cm from the vaginal mucosa. RESULTS: Patients with HDR-brachytherapy alone showed a 5-year survival of 94.3% for Stage I and 73.6% for Stage II (p = 0.0007). Patients who received both brachytherapy and additional external pelvic irradiation had a 5-year survival of 94.1% for Stage I, 81.1% for Stage II, 70.4% for Stage III and 46.9% for Stage IV (p = 0.0001). The main predictors for survival in a multivariate analysis were stage and grading. Patients with combined radiotherapy had a local recurrence rate of 3.2%, whereas patients with brachytherapy alone who were better selected and had more favorable prognostic factors showed a recurrence rate of 2%. Low-risk patients (Stage I, Grade 1, low infiltration) in the HDR-brachytherapy group had 6 relapses, mainly caused by insufficient treatment on the basis of papillary histology. High-risk patients with poorly differentiated tumors, which infiltrate more than half the myometrial wall might benefit from additional external radiotherapy in terms of reduction of local recurrence and better survival. Five-year actuarial survival rate was 93.6% after combined radiotherapy vs 86.7% after brachytherapy alone. Complications were graded according to the RTOG scoring system. Severe late complications were fistulas of bladder and/or bowel, which occurred in 2.8% in the combined radiotherapy group, and 0.7% in the HDR brachytherapy group. CONCLUSIONS: Low-risk patients should be generally treated postoperative with HDR-brachytherapy alone. Combined radiotherapy decreased pelvic relapses for high-risk patients with overall low complication rates. We conclude that an individually adjusted postoperative radiotherapy allows a well tolerated treatment with excellent results.

Brachytherapy

Radiotherapy in Ewing's sarcoma and PNET of the chest wall: results of the trials CESS 81, CESS 86 and EICESS 92.

PURPOSE: Treatment results and the pattern of relapse were evaluated in the multimodal treatment of Ewing's sarcomas of the chest wall. METHODS AND MATERIALS: In a retrospective analysis, 114 patients with non-metastatic Ewing's sarcoma of the chest wall were evaluated. They were treated in the CESS 81, CESS 86, or EICESS 92 studies between January 1981 and December 1993. The treatment consisted of polychemotherapy (VACA, VAIA, or EVAIA) and local therapy, either surgery alone (14 patients), radiotherapy alone (28 patients) or a combination of both (71 patients). The median follow-up was 46.6 months (range 5-170). A relapse analysis for all patients with local or combined relapses was performed. RESULTS: Overall survival was 60% after 5 years, event-free survival was 50%. Thirty-seven patients had a systemic relapse (32.4%), 11 patients had a local relapse alone (9.6%), and 3 patients had a combined local and systemic relapse (2.6%). The risk to relapse locally after 5 years was 0% after surgery alone, 19% after radiation alone, and 19% after postoperative irradiation. None of the 8 patients with preoperative irradiation have failed locally so far. With the introduction of central radiotherapy planning in CESS 86, local control of irradiated patients improved. Ten of 14 patients with local failure could be evaluated in the relapse analysis: 3 patients had an in-field relapse, 4 patients had a marginal relapse, 2 patients had a relapse outside the radiation fields, and 1 patient failed with pleural dissemination. Six treatment deviations were observed. CONCLUSION: Local control was best after surgery alone in a positively selected group of patients. Local control after radiation or combined radiation and surgery was good. With diligent performance of radiotherapy, it will be possible to further improve the results in the radiotherapy group.

Antineoplastic Combined Chemotherapy Protocols

Second malignancies after treatment for Ewing's sarcoma: a report of the CESS-studies.

PURPOSE: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. MATERIALS AND METHODS: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n = 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. RESULTS: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clinical remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1 % (3/328) of all deaths in the CESS-studies. CONCLUSIONS: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5 % after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.

Antineoplastic Combined Chemotherapy Protocols

Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue.

BACKGROUND: Most previous oxygenation measurements of head and neck tumors have mainly been performed in neck nodes. We investigated, therefore, the relationship between the pO2 status of primary tumors, cervical neck node metastases and normal tissues. PATIENTS AND METHODS: 30 patients with histologically proven advanced stage III-IV squamous cell carcinoma of head and neck underwent pretreatment polarographic pO2 measurements with a pO2 histograph (Eppendorf, Hamburg, Germany). We obtained data on oxygenation of 23 primary tumors, of 22 neck node metastases, and of 30 contralateral sternocleidomastoid muscles. In 15 cases, we were able to perform measurements in all three regions in the same individual. results: A highly significant correlation existed between the median pO2 of primary tumors and their neck node metastases (p=0.0001), as well as between the proportion of pO2 values < or =2.5 mmHg and +/-5.0 mmHg (p=0.0001, p=0.001) in both anatomic sites. The average pretreatment median PO2 was 14.7 mmHg (range 0.2-58.5 mmHg) in primary tumors, 13.7 mmHg (range 1.9-50.3 mmHg) in neck node metastases, and 43.8 mmHg (range 20.8-67.7 mmHg) in sternocleidomastoid muscles. In all cases, the oxygenation of malignant tissue was below that of the corresponding muscle. There was also a weak, but significant, correlation between hemoglobin level and the median pO2 of the primary tumors, as well as between hemoglobin concentration and the proportion of values below 5 mmHg at the primary site (p=0.017, p=0.003). CONCLUSIONS: Primary tumors and their regional lymph node metastases in advanced squamous cell carcinoma of the head and neck show comparable patterns of oxygenation in terms of the median pO2 and the proportion of hypoxic measurements. This report suggests that, in patients with such carcinomas, the oxygenation data obtained at one site are related to tumor oxygenation at other sites, so that measurements in any anatomic site would be sufficient to estimate a tumor's oxygenation status. The weak correlation between pO2 and hemoglobin level requires further investigation.

Adult

A 2-week pretreatment with 13-cis-retinoic acid + interferon-alpha-2a prior to definitive radiation improves tumor tissue oxygenation in cervical cancers.

BACKGROUND: We have evaluated the tumor tissue pO2 in cervical cancers in patients treated with 13-cis-retinoic acid and interferon-alpha-2a prior to and during radiotherapy. PATIENTS AND METHODS: From June 1995 through April 1997, 22 patients with squamous cell carcinoma FIGO IIB/III of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-alpha-2a (IFN-alpha-2a) as part of a phase-II protocol. cRA/IFN-alpha-2a started 14 days prior to radiotherapy (1 mg per kilogramme body weight cRA orally daily plus 6 x 10(6) IU IFN-alpha-2a subcutaneously daily). After this induction period, standard radiotherapy was administered (external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus HDR-brachytherapy). During radiotherapy, cRA/IFN-alpha-2a treatment was continued with 50% of the daily doses. Tumor tissue pO2-measurements were performed prior to and after the cRA/IFN-induction period as well as at 20 Gy and at the end of radiotherapy with an Eppendorf-pO2-histograph. RESULTS: In 11 out of the 22 patients, pO2-measurements were performed prior to the cRA/IFN-induction therapy. The median pO2 of these untreated tumors was 17.7 +/- 16.3 mm Hg. The relative frequency of hypoxic readings with pO2-values below 5 mm Hg ranged from 0% to 60.6% (mean 24.3 +/- 21.0%). After the 2-week induction period with cRA/IFN, the median pO2 had increased from 17.7 +/- 16.3 mm Hg to 27.6 +/- 19.1 mm Hg (not significant). In all 5 patients with hypoxic tumors prior to cRA/IFN (median pO2 of 10 mm Hg or less), the median pO2 was above 20 mm Hg after the 2-week cRA/IFN-induction. In this subgroup of hypoxic tumors, the median pO2 increased from 6.3 +/- 2.7 mm Hg to 27.0 +/- 5.6 mm Hg (p = 0.004, t-test for paired samples). The frequency of hypoxic readings (pO2-values < 5 mm Hg) decreased from 44.7 +/- 17.1% to 2.0 +/- 2.5% (p = 0.012, t-test for paired samples). There was, however, no obvious volume reduction after 14 weeks of cRA/IFN on clinical examination. A complete clinical remission of the local tumor was observed in 19/22 patients after radiotherapy and additional cRA/IFN-alpha-2a-treatment. In primarily hypoxic tumors (with a median pO2 below 10 mm Hg prior to treatment), 4/5 achieved complete remission. CONCLUSIONS: Pretreatment with cRA/IFN improves oxygenation of primarily hypoxic cervical cancers. The mechanisms of action remain unclear and further investigation of the combination regimen is recommended.

Aged