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Few birth defects in offspring of cancer survivors
SCIENCE AND MEDICINE
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ne of the most hotly debated questions at the Society of Gynecologic Oncologists meeting (Feb 7–11; Orlando, FL, USA) was: “Is a single modality therapy sufficient for treatment of high-risk cervical cancer?” Early results from Gynecologic Oncology Group trials indicate that the answer may be no. Peter Rose (University Hospital, Cleveland, OH, USA) reported that weekly cisplatinum (CDDP) therapy plus radiotherapy is associated with a lower rate of pelvic recurrence, and maybe a higher survival rate, than is hydroxyurea therapy plus radiotherapy. CDDP is better tolerated than a combination of CDDP, 5-fluorouracil, and hydroxyurea when used with radiotherapy in advanced cervical cancer. According to Alexander Sedlis (SUNY Health Science Center, Brooklyn, NY, USA), postoperative radiotherapy reduces the risk of recurrence of high-risk, nodenegative stage 1b cervical cancer but causes severe gastrointestinal and genitourinary toxicity in 2·9% of cases. Finally, Henry Keys (Albany Medical College, Albany, NY, USA) reported that addition of weekly CDDP to radiotherapy followed by adjuvant hysterectomy for bulky stage 1 cancers may improve the recurrence-free interval and survival rate compared with radiotherapy and hysterectomy alone. None of these trials is sufficiently mature to yield relative survivals. However, the results confirm what many gynaecological oncologists already believe—namely, that single modality therapy is insufficient for high-risk cervical cancer—and may provide impetus to change the standard of care. Spontaneous regression of cervical intraepithelial neoplasia (CIN) is well documented and women who present with CIN during pregnancy are usually just watched carefully. Reporting on a study on 108 women, David Ahdoot (University of California at Irvine, CA, USA) confirmed regression of CIN during pregnancy, adding that regression rates were significantly higher for high-grade CIN after vaginal delivery than after caesarean section. Whether this is a mechanical phenomenon or a result of postpartum cervical healing is uncertain.
Carolyn Johnston
652
Few birth defects in offspring of cancer survivors he largest and most comprehensive study so far to look for birth defects in children born to survivors of childhood cancers gives reassurance that cancer treatment, or at least the use of older protocols, does not carry a large risk for genetic disease. The frequency of congenital abnormalities and genetic diseases was measured among 2198 children of people treated before 1976 for a malignancy during childhood or adolescence. Data were collected from five US cancer centres (Am J Hum Genet 1998; 62: 45–52; http://www. journals.uchicago.edu/AJHG/jounal/). Genetic disease occurred in 3·4% of the offspring of childhood-cancer survivors compared with 3·1% of the 4544 offspring of controls—a nonsignificant difference. There were no
T
differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with those not treated this way showed no association with sporadic genetic disease. The principal author of the study, Julieanne Byrne (now at the Boyne Research Institute, Ireland), notes that “The importance of a study such as this one is the use it will have in counselling cancer survivors”. However, many of the therapies in this study are out of date, she adds, so scientists will now have to wait decades to evaluate the latest therapies used to treat childhood cancers. Karen Birchard
Schizophrenia’s complexities begin to yield esearchers meeting this month in Davos, Switzerland, for the Ninth Biennial Winter Workshop on Schizophrenia (Feb 7–13) discussed aspects of the illness from the latest on brain function to therapy. The current model of brain function proposes that activations occur over widely Seeing is believing disparate areas and are coordinated with reciprocal inhibitions occurring elsewhere. P Liddle (University of British Columbia, Vancouver, Canada) showed how this task-dependent activity pattern is disturbed in schizophrenia to such an extent that a pattern-recognition algorithm can be successfully used to categorise schizophrenia from positron-emission-tomography data. In support of this, T Koenig (University Hospital of Psychiatry, Zurich, Switzerland) reported how summation of electroencephalographic potentials reveals prolongation of an unusual brain state in people with schizophrenia. The traditional view that schizophrenia involves dopaminergic hyperactivity is giving way to a more complex scenario. The new successful atypical neuroleptics target serotonergic pathways as well as dopaminergic pathways. Several delegates proposed that the excitatory and neurodestructive effects of gluta-
R
mine may be aetiological components in the disease process. Among the evidence presented for this idea was that given by L Garey (Imperial College School of Medicine, London, UK) which showed that glutaminergic spines on pyramidal cells are lost in schizophrenic patients. Other delegates showed underactivity of the glutaminergic-modulating, inhibitory ␥-aminobutyric acid interneurons. Such interneurons are sparse in the frontal cortices of schizophrenic patients and frontal underactivity is often found in neuroimaging studies. Disease progression is being charted in several cohorts of first episode, untreated patients and in patients at a high genetic risk of developing schizophrenia. Increasing evidence suggests that the illness should be treated early. The advent of atypical neuroleptics with fewer side-effects than older drugs and evidence of improvement in cognitive and motor function, and reduction in hostility and aggression, make the early use of drugs more acceptable. However, problems remain, including indistinct initial symptoms and inadequate GP prescribing, problems that may be solved by improved clinician education. Science Photo Library
Multiple therapies hit cervical cancer best
Malcolm Weller
THE LANCET • Vol 351 • February 28, 1998
O
ne of the most hotly debated questions at the Society of Gynecologic Oncologists meeting (Feb 7–11; Orlando, FL, USA) was: “Is a single modality therapy sufficient for treatment of high-risk cervical cancer?” Early results from Gynecologic Oncology Group trials indicate that the answer may be no. Peter Rose (University Hospital, Cleveland, OH, USA) reported that weekly cisplatinum (CDDP) therapy plus radiotherapy is associated with a lower rate of pelvic recurrence, and maybe a higher survival rate, than is hydroxyurea therapy plus radiotherapy. CDDP is better tolerated than a combination of CDDP, 5-fluorouracil, and hydroxyurea when used with radiotherapy in advanced cervical cancer. According to Alexander Sedlis (SUNY Health Science Center, Brooklyn, NY, USA), postoperative radiotherapy reduces the risk of recurrence of high-risk, nodenegative stage 1b cervical cancer but causes severe gastrointestinal and genitourinary toxicity in 2·9% of cases. Finally, Henry Keys (Albany Medical College, Albany, NY, USA) reported that addition of weekly CDDP to radiotherapy followed by adjuvant hysterectomy for bulky stage 1 cancers may improve the recurrence-free interval and survival rate compared with radiotherapy and hysterectomy alone. None of these trials is sufficiently mature to yield relative survivals. However, the results confirm what many gynaecological oncologists already believe—namely, that single modality therapy is insufficient for high-risk cervical cancer—and may provide impetus to change the standard of care. Spontaneous regression of cervical intraepithelial neoplasia (CIN) is well documented and women who present with CIN during pregnancy are usually just watched carefully. Reporting on a study on 108 women, David Ahdoot (University of California at Irvine, CA, USA) confirmed regression of CIN during pregnancy, adding that regression rates were significantly higher for high-grade CIN after vaginal delivery than after caesarean section. Whether this is a mechanical phenomenon or a result of postpartum cervical healing is uncertain.
Carolyn Johnston
652
Few birth defects in offspring of cancer survivors he largest and most comprehensive study so far to look for birth defects in children born to survivors of childhood cancers gives reassurance that cancer treatment, or at least the use of older protocols, does not carry a large risk for genetic disease. The frequency of congenital abnormalities and genetic diseases was measured among 2198 children of people treated before 1976 for a malignancy during childhood or adolescence. Data were collected from five US cancer centres (Am J Hum Genet 1998; 62: 45–52; http://www. journals.uchicago.edu/AJHG/jounal/). Genetic disease occurred in 3·4% of the offspring of childhood-cancer survivors compared with 3·1% of the 4544 offspring of controls—a nonsignificant difference. There were no
T
differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with those not treated this way showed no association with sporadic genetic disease. The principal author of the study, Julieanne Byrne (now at the Boyne Research Institute, Ireland), notes that “The importance of a study such as this one is the use it will have in counselling cancer survivors”. However, many of the therapies in this study are out of date, she adds, so scientists will now have to wait decades to evaluate the latest therapies used to treat childhood cancers. Karen Birchard
Schizophrenia’s complexities begin to yield esearchers meeting this month in Davos, Switzerland, for the Ninth Biennial Winter Workshop on Schizophrenia (Feb 7–13) discussed aspects of the illness from the latest on brain function to therapy. The current model of brain function proposes that activations occur over widely Seeing is believing disparate areas and are coordinated with reciprocal inhibitions occurring elsewhere. P Liddle (University of British Columbia, Vancouver, Canada) showed how this task-dependent activity pattern is disturbed in schizophrenia to such an extent that a pattern-recognition algorithm can be successfully used to categorise schizophrenia from positron-emission-tomography data. In support of this, T Koenig (University Hospital of Psychiatry, Zurich, Switzerland) reported how summation of electroencephalographic potentials reveals prolongation of an unusual brain state in people with schizophrenia. The traditional view that schizophrenia involves dopaminergic hyperactivity is giving way to a more complex scenario. The new successful atypical neuroleptics target serotonergic pathways as well as dopaminergic pathways. Several delegates proposed that the excitatory and neurodestructive effects of gluta-
R
mine may be aetiological components in the disease process. Among the evidence presented for this idea was that given by L Garey (Imperial College School of Medicine, London, UK) which showed that glutaminergic spines on pyramidal cells are lost in schizophrenic patients. Other delegates showed underactivity of the glutaminergic-modulating, inhibitory ␥-aminobutyric acid interneurons. Such interneurons are sparse in the frontal cortices of schizophrenic patients and frontal underactivity is often found in neuroimaging studies. Disease progression is being charted in several cohorts of first episode, untreated patients and in patients at a high genetic risk of developing schizophrenia. Increasing evidence suggests that the illness should be treated early. The advent of atypical neuroleptics with fewer side-effects than older drugs and evidence of improvement in cognitive and motor function, and reduction in hostility and aggression, make the early use of drugs more acceptable. However, problems remain, including indistinct initial symptoms and inadequate GP prescribing, problems that may be solved by improved clinician education. Science Photo Library
Multiple therapies hit cervical cancer best
Malcolm Weller
THE LANCET • Vol 351 • February 28, 1998