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C M Balch

Publications and source records attributed to C M Balch.

At least 37 records · Page 2Linked to original sources

Factors affecting survival following local, regional, or distant recurrence from localized melanoma.

BACKGROUND AND OBJECTIVES: Approximately one third of all melanoma patients will experience disease recurrence. Factors that affect patient survival following local, regional, or distant first recurrences of localized melanoma are the subject of this investigation. METHODS: Survival times for a total of 1,085 first recurrences from 4,568 localized melanoma patients were examined in relationship to patient and disease factors by Cox regression. Nearly half (48.8%) of all first recurrences were regional, 21.8% were local, and 29.4% were distant recurrences. RESULTS: Survival following recurrence differed significantly by site of recurrence (local, regional, or distant; P < 0.0001). Within each site, the median survival time did not differ by time of recurrence following diagnosis. Significant tumor factors for survival following local recurrence included tumor thickness (P = 0.0263) and lesion location (P < 0.0001). For regional recurrences, survival was significantly related to ulceration (P = 0.0105) and whether the recurrence was combined with a local recurrence (P = 0.0429). Survival following distant metastasis was related to number of distant sites (P < 0.0001) and whether a visceral site was involved (P < 0.0001). CONCLUSIONS: Patient and tumor characteristics predict survival following recurrence. Regardless of disease-free interval, long-term follow-up of melanoma patients is necessary. Patients experiencing distant metastasis have the shortest median survival time compared to patients experiencing local or regional recurrences.

Disease-Free Survival↗

Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection.

BACKGROUND: Antibiotic prophylaxis is controversial in patients undergoing axillary lymph node dissection (ALND). We determined whether preoperative antibiotics decreased incidence or treatment cost of infectious complications following ALND. METHODS: Two hundred patients entered this prospective, randomized, double-blind trial. Patients received either placebo or cefonicid preoperatively. Loco-regional signs of infection were monitored for 4 weeks postoperatively. RESULTS: There was a trend toward fewer infections in the prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid significantly decreased severe infections requiring hospitalization (placebo 8% versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of infection per patient ($49.80 versus $364.87). CONCLUSIONS: We demonstrated a trend toward fewer overall infections and significantly fewer severe infections in patients given prophylactic antibiotics, which translated into a decrease in the cost of treatment for infectious complications. These findings support antibiotic prophylaxis for patients undergoing ALND.

Adult↗

Clinical outcomes of localized melanoma of the foot: a case-control study.

The controversy over whether melanoma of the foot has a poorer prognosis than melanoma of the leg remains unresolved. This investigation used a case-control design to address this issue. This design consisted of a survival analysis of 119 cases with localized melanoma of the foot and 238 controls with localized melanoma of the leg that were matched on prognostic factors including tumor thickness, ulceration, surgical treatment, gender, year of diagnosis, and age. There was a statistically significant difference between the survival rates of cases and controls. The 5-year survival rate for cases was 74.3% compared to 85.2% for controls. At 10 years, the survival rate was 63.6% for cases and 77.2% for controls. Cases experienced a higher percentage of distant recurrences than controls. These results imply that patients with melanoma of the foot have a poorer survival than patients with melanoma of the leg after controlling for prognostic factors.

Adult↗

Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial.

BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets-men aged 44-57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease-showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 1996 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. STUDY DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x 10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44-57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.

Adolescent↗

Is the capacity for lymph node-mediated distant dissemination the same for all nodal groups in malignant melanoma?

This study addresses two hypotheses: (1) that the inherent potential of melanoma metastatic to regional nodal groups for lymph-mediated distant dissemination may not be the same for all nodal groups; and (2) that the risk of distant metastases in patients with clinically involved nodal metastases is higher than in patients with clinically occult nodal metastases. It involved a retrospective chart review of patients with histologically involved axillary or inguinal nodes treated at Roswell Park Cancer Institute (RPCI) (244 patients) or at the participating institutes from the Intergroup Surgical Trial (IST) (108 patients). The distant recurrence rates of 623 melanomas with axillary or inguinal drainage from the IST data were also reviewed. In the RPCI data there was a significant difference in the overall and disease-free survival (P=0.0001) between patients with microscopic versus palpable involvement of the regional nodes in the axilla, while no such difference was observed for patients with groin metastases (P=0.30 and 0.36, respectively). The same trend was noted in the IST data. In the latter data the distant recurrence rate for melanomas drained via the axilla was significantly higher (P=0.026) than for those drained by the groin. In conclusion, lymph-mediated distant dissemination may be more aggressive from the axilla than from the groin in melanoma.

Axilla↗

Prognostic factors for survival of patients treated systemically for disseminated melanoma.

PURPOSE: The current American Joint Commission on Cancer (AJCC) staging system distinguishes between soft tissue and visceral metastases in advanced (stage IV) melanoma. We sought to verify these staging criteria and to identify prognostic variables that could be used to evaluate the impact of systemic therapy on long-term survival during the prior decade. PATIENTS AND METHODS: We conducted a retrospective study of patients with advanced cutaneous melanoma enrolled in clinical trials between 1979 and 1989 at The University of Texas M.D. Anderson Cancer Center. Pretreatment age, sex, number of organs with metastases, serum levels of lactate dehydrogenase (LDH) and albumin, and period of enrollment were analyzed using a Cox proportional hazards model of survival. RESULTS: In univariate and multivariate analyses that involved 318 stage IV patients, normal serum levels of LDH and albumin, soft tissue and/or single visceral organ metastases (especially lung), female sex, and enrollment late in the decade were independent positive predictors for survival. In multivariate analyses, the current AJCC criteria did not significantly predict outcome. Systemic treatment response did not bias these results, and only 4% of patients had a complete response. Patients who lived more than 2 years (11%) had a mix of favorable prognostic characteristics and a high frequency of systemic or surgically induced complete response. CONCLUSION: This study supports the use of stratification parameters that reflect the favorable prognostic impact of soft tissue or single visceral organ metastases and normal serum levels of LDH and albumin at time of enrollment in advanced melanoma trials. Improved survival over the prior decade probably reflects advances in diagnostic and palliative interventions.

Adult↗

Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma.

PURPOSE: To determine the patterns of recurrence and causes of regional nodal basin failure in stage I or II melanoma patients who had a histologically negative sentinel lymph node (SLN) and whose regional nodal basins were not dissected following lymphatic mapping and SLN biopsy. PATIENTS AND METHODS: The records of 344 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1995 at The University of Texas M.D. Anderson Cancer Center were reviewed. Of 322 patients who underwent successful lymphatic mapping procedures, 270 had histologically negative SLNs; mapped nodal basins were observed without further surgical intervention in 243 of these 270 patients. Recurrence patterns were analyzed from this cohort and a histologic reevaluation of all previously identified SLNs on which a biopsy had been taken was performed in patients who developed recurrent disease. RESULTS: Of 243 patients with a histologically negative SLN, 27 (11%) developed local, in-transit, regional nodal, and/or distant metastases after a median follow-up time of 35 months. Ten patients (4.1%) developed a nodal recurrence in the previously mapped basin, either solely or as a component of the first site of recurrence. Detailed analysis of the SLNs in these 10 patients demonstrated evidence of occult metastases in 80% by serial sectioning or immunohistochemical staining. CONCLUSION: Regional nodal failures in melanoma patients following a negative SLN biopsy are infrequent and to date have most commonly occurred because conventional histologic evaluation was unable to identify occult metastatic disease. These data provide further evidence that lymphatic mapping and SLN biopsy accurately reflect the status of the regional nodal basin. Specialized pathologic techniques are necessary to reduce further the already low false-negative rates and to improve disease staging.

Adolescent↗

Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma.

Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.

Adjuvants, Immunologic↗

Classification of localized melanoma by the exponential survival trees method.

BACKGROUND: Over the past 2 decades, remarkable progress has been made in the identification of clinical and pathologic factors that affect the survival of patients with melanoma. Through the use of multivariate regression methods, key prognostic factors, such as tumor thickness, tumor ulceration, invasion level, and lesion location, have been identified. Clinical investigators are often interested in developing criteria to classify melanoma patients into different risk groups based on the key prognostic factors identified. However, classical multivariate regression models are generally less efficient in accomplishing this task than newly developed tree-based methods. METHODS: In this study, the authors applied the exponential survival trees method to analyze a combined data set (n = 4568) from the University of Alabama at Birmingham and the Sydney Melanoma Unit in Camperdown, Australia. A survival tree was created according to prognostic factors that classified patients into homogeneous subgroups by survival. Six clinical and pathologic factors were included in the analysis. This tree-based method provided a superior means of prognostic classification and was shown to have greater ability to detect interactions among the variables than regression models. RESULTS: Tumor thickness was found to be the most important prognostic factor, followed by tumor ulceration and primary lesion site. Some important interactions among these prognostic factors were identified. Five distinct risk groups, defined by tumor thickness, ulceration, and primary lesion site, were created. Patients who had tumor thickness less than or equal to 0.75 mm and lesions on their arms or legs had the best prognosis. Patients who had ulcerated tumors with thickness greater than 4.50 mm had the poorest prognosis. CONCLUSIONS: The authors' analysis, based on exponential survival trees, provides a comprehensive, easy-to-use risk grouping system for classifying patients with localized melanoma. This grouping system would be useful in the clinical management of melanoma patients and in designing and analyzing clinical trials.

Decision Trees↗

Recent advances in the care of the patient with malignant melanoma.

OBJECTIVE: The authors review the recent advances in the surgical care, staging, and adjuvant treatment of the patient with melanoma. SUMMARY BACKGROUND DATA: Melanoma care has not changed significantly in the last 20 years, and the controversy of elective lymph node dissections in this disease continues to be discussed. Two advances in the care of the patient with melanoma have occurred in the last 3 years to make this an exciting time for clinicians and to offer more hope for the patients with this disease. The concept of the sentinel lymph node (SLN), defined by Morton as the first node in the lymphatic basin that drains the primary melanoma, has been documented to contain the first site of metastatic disease. This technology can be used to stage nodally the melanoma patient, identifying the subgroup of patients (stage III) who have a 5-year survival rate less than 50%. Members of this group are candidates for effective adjuvant therapies. METHODS: A review of the surgical techniques of melanoma care, including recently reported new studies of elective node dissection (ELND) and SLN biopsy in patients with melanoma was performed. In addition, the Eastern Cooperative Oncology Group (ECOG) 1684 trial, which was the basis for the Food and Drug Administration approval of adjuvant interferon-alpha-2b (IFN-alpha-2b) is discussed. RESULTS: The Intergroup Melanoma Trial has reported a survival benefit for performing ELND in patients with melanoma and tumor thickness between 1 and 2 mm or in patients that are younger than 60 years of age. With six reports in the literature that show there is an order to melanoma nodal metastases and that the SLN histology is reflective of the histology of the remainder of the nodal basin, the more conservative SLN biopsy can be performed to adequately stage nodally the patient with melanoma. Patients with nodal metastases who are rendered free of disease with surgical resection have the most to benefit from adjuvant IF-alpha-2b. If one considers only the lymph node-positive group of patients, the survival benefit associate with adjuvant IFN is significant (p = 0.008). CONCLUSIONS: New standards of care for the melanoma patient have been established. Patients at high risk for recurrence have been shown to experience a survival benefit with adjuvant IFN-alpha-2b. With these data, the argument can be made that all patients with melanoma greater than 1 mm should have a nodal staging procedure. Selective lymphadenectomy with SLN biopsy is the least morbid procedure that can be used to obtain this information. If surgeons do not have the nuclear medicine or pathology support to perform lymphatic mapping, then the guidelines of the Intergroup Melanoma Study should be used to apply ELND in a selective fashion. In this way, patients are identified with micrometastatic disease early in their clinical course and can be offered the survival benefit of adjuvant therapy.

Antineoplastic Agents↗

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial.

OBJECTIVE: The efficacy of vaccinia melanoma oncolysate (VMO) vaccine to increase overall survival and disease-free survival of patients with surgically resected International Union Against Cancer (UICC) stage II melanoma was studied in a phase III, randomized, multi-institutional trial. SUMMARY BACKGROUND DATA: Phase I and II trials with VMO showed minimal toxicity and clinical efficacy in patients with melanoma. In a recently completed phase III VMO trial, the first interim analysis performed in April 1994 showed an increasing trend in the survival of patients treated with VMO. The second interim analysis was performed in April 1995. METHODS: Patients with surgically resected stage II (UICC) melanoma were treated with VMO (N = 104) or placebo vaccinia vaccine virus (V) (N = 113) once a week for 13 weeks and then once every 2 weeks for a total of 12 months. Patients' clinical data were collected as of May 1995 and analyzed for survival. RESULTS: In this second interim analysis, the mean follow-up time is 42.28 months. No survival difference was observed between VMO and V treatments. However, in a retrospective subset analysis, a subset of males between the ages of 44 and 57 years and having one to five positive nodes (at 2-, 3-, and 5-year intervals, 13.6%, 15.9%, and 20.3% difference insurvival in favor of VMO [N = 20] when compared to V [N = 18] [p = 0.037]) and another subset of patients with clinical stage I (at 3- and 5-year intervals, 30% and 7% difference in survival in favor of VMO [N = 20] when compared to V [N = 23], [p = 0.05]) showed significant survival advantage with VMO. CONCLUSIONS: Although VMO vaccine therapy in surgical adjuvant setting did not produce a significant survival benefit to all patients with melanoma, patients from the above two subsets had significant survival benefit.

Adult↗

Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system.

PURPOSE: To critically review the accuracy of the current American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma and propose a more useful staging system. METHODS: Retrospective evaluation of the published data as well as a reanalysis of the University of Alabama and Sydney Melanoma Unit (UAB/SMU) data bases (n = 4,568) for patients with primary melanoma was performed to examine specifically the impact of level of invasion and ulceration on the prognostic value of tumor thickness. In addition, an overlay graphic technique was used to compare the Kaplan-Meier survival curves of patients with local recurrences, satellites, in-transit metastases, and nodal metastases reported in the literature. RESULTS: Tumor thickness and ulceration remained the most powerful prognostic indicators in patients with stage I and II disease. Level of invasion provided statistically significant prognostic information only in the subgroup of patients with tumor thickness < or = 1 mm, but the absolute 10-year survival differences were small and inconsistent (level II, 95%; level III, 85%; level IV, 89%). The best statistical fit for tumor thickness cutoffs was at 1 versus 2 versus 4 mm. The overlay graphic technique showed that patients who developed satellite lesions or local recurrence had prognoses similar to those of patients with stage III disease. The most important prognostic factor for patients with nodal metastases was number of involved nodes rather than size. CONCLUSION: Our analysis showed that the current AJCC staging system has many inaccuracies that should be modified to conform to published data. On the basis of our analysis and review of the literature, we propose a new and more accurate staging system.

Humans↗

Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial.

BACKGROUND: In the past, radical margins of excision were prescribed for cutaneous melanoma based on preconceived notions rather than on hard clinical evidence. METHODS: In a prospective study of 742 patients with intermediate-thickness melanoma (1-4 mm), 470 patients with trunk or proximal extremity lesions were randomized into a 2- or 4-cm margin. Patients with distal extremity or head and neck lesions (n = 272) received uniformly a 2-cm margin. RESULTS: The overall rate of local recurrence was 3.8%. This rate in the randomized portion (n = 470) was 2.1% for the 2-cm margin and 2.6% for the 4-cm margin (p = 0.72). A progressive increase in local recurrence rates was observed with thickness: 2.3% for lesions 1.0-2.0 mm, 4.2% for those 2.01-3.0 mm, and 11.7% for those 3.01-4.0 mm thick (p = 0.001). Local recurrence occurred in 1.5% of those without ulceration and in 10.6% of those with ulceration of the primary lesion (p = 0.001). The local recurrence rate was not significantly affected by the margin of resection even among the thicker or ulcerated lesions. It also was not affected significantly by the method of closure of the primary site or management of the regional nodes, or the age or gender of the patients. CONCLUSIONS: A 2-cm margin is as effective as a 4-cm margin in local control and survival of intermediate-thickness melanomas. The local recurrence rate is significantly affected by the thickness of the primary lesion and the presence or not of ulceration.

Adolescent↗

Cranial irradiation after surgical excision of brain metastases in melanoma patients.

BACKGROUND: Brain metastases account for 20-54% of reported deaths from melanoma. Duration and quality of survival depend on the extent of metastatic disease and response to treatment. Treatment goals are palliation of symptoms and prolongation of life. No studies have directly compared surgery alone and surgery with adjunctive cranial irradiation in patients with solitary brain metastases. METHODS: We evaluated postoperative adjunctive cranial irradiation in 34 patients with solitary brain metastases. RESULTS: Overall survival was significantly improved in the 22 patients who received adjunctive cranial irradiation versus that in the 12 patients who had surgery alone. Twenty-eight patients subsequently relapsed. Nine of 10 patients with surgery alone had brain recurrence as a component of failure. Six of 10 patients not receiving irradiation had brain recurrences as a component of relapse at multiple sites whereas only 1 of 18 patients receiving irradiation relapsed with the brain. CONCLUSIONS: Adjunctive cranial irradiation is justified for melanoma patients who undergo surgical therapy for solitary brain metastases. Survival in patients presenting with solitary brain metastases was improved by a reduction of relapse in the brain as a component of failure by combined surgery and irradiation.

Adult↗

Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger.

OBJECTIVE: A prospective multi-institutional randomized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective (immediate) lymph node dissection (ELND) for intermediate-thickness melanoma (1-4 mm) improves survival rates compared with clinical observation of the lymph nodes. A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND. METHODS: The eligible patients were stratified according to tumor thickness, anatomic site, and ulceration, and then were prerandomized to either ELND or nodal observation. Femoral, axillary, or modified neck dissections were performed using standardized surgical guidelines. RESULTS: The median follow-up was 7.4 years. A multifactorial (Cox regression) analysis showed that the following factors independently influenced survival: tumor ulceration, trunk site, tumor thickness, and patient age. Surgical treatment results were first compared based on randomized intent. Overall 5-year survival was not significantly different for patients who received ELND or nodal observation. However, the 552 patients 60 years of age or younger (75% of total group) with ELND has a significantly better 5-year survival. Among these patients, 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick, the 403 patients without tumor ulceration, and the 284 patients with tumors 1 to 2 mm thick and no ulceration. In contrast, patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation. When survival rates were compared based on treatment actually received (i.e., including crossover patients), the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick, those without tumor ulceration, and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration. CONCLUSION: This is the first randomized study to prove the value of surgical treatment for clinically occult regional metastases. Patients 60 years or age or younger with intermediate-thickness melanomas, especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick, may benefit from ELND. However, because some patients still are developing distant disease, these results should be considered an interim analysis.

Female↗